RESUMO
Realizing Effectiveness Across Continents with Hydroxyurea (REACH, NCT01966731) provides hydroxyurea at maximum tolerated dose (MTD) for children with sickle cell anemia (SCA) in sub-Saharan Africa. Beyond reducing SCA-related clinical events, documented treatment benefits include â¼50% reduction in malaria incidence. To identify associations and propose mechanisms by which hydroxyurea could be associated with lower malaria rates, infections were recorded across all clinical sites (Angola, Democratic Republic of Congo, Kenya, and Uganda). Hazard ratios (HR) with 95% confidence intervals (CIs) for baseline demographics, and time-varying laboratory and clinical parameters were estimated in a modified Cox gap-time model for repeated events. Over 3387 patient-years of hydroxyurea treatment, 717 clinical malaria episodes occurred in 336 of 606 study participants; over half were confirmed by blood smear and/or rapid diagnostic testing with 97.8% Plasmodium falciparum. In univariate analysis limited to 4 confirmed infections per child, malaria risk was significantly associated with absolute neutrophil count (ANC), splenomegaly, hemoglobin, and achieving MTD; age, malaria season, MTD dose, fetal hemoglobin, α-thalassemia, and glucose-6-phosphate dehydrogenase deficiency had no effect. In multivariable regression of confirmed infections, ANC was significant (HR, 1.37 per doubled value; 95% CI, 1.10-1.70; P = .0052), and ANC values <3.0 × 109/L were associated with lower malaria incidence. Compared with nonpalpable spleen, 1- to 4-cm splenomegaly also was associated with higher malaria risk (HR, 2.01; 95% CI, 1.41-2.85; P = .0001). Hydroxyurea at MTD is associated with lower malaria incidence in SCA through incompletely defined mechanisms, but treatment-associated mild myelosuppression with ANC <3.0 × 109/L is salutary. Splenomegaly is an unexplained risk factor for malaria infections among children with SCA in Africa.
Assuntos
Anemia Falciforme , Malária , Humanos , Criança , Hidroxiureia/efeitos adversos , Incidência , Esplenomegalia/epidemiologia , Esplenomegalia/tratamento farmacológico , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/epidemiologia , Malária/tratamento farmacológico , Malária/epidemiologia , Malária/prevenção & controle , África Subsaariana/epidemiologiaRESUMO
Children with sickle cell anemia (SCA) in Africa frequently require transfusions for SCA complications. Despite limited blood supplies, strategies to reduce their transfusion needs have not been widely evaluated or implemented. We analyzed transfusion utilization in children with SCA before and during hydroxyurea treatment. REACH (Realizing Effectiveness Across Continents with Hydroxyurea, NCT01966731) is a longitudinal Phase I/II trial of hydroxyurea in children with SCA from Angola, Democratic Republic of Congo, Kenya, and Uganda. After enrollment, children had a two-month pre-treatment screening period followed by 6 months of fixed-dose hydroxyurea (15-20 mg/kg/day), 18 months of dose escalation, and then stable dosing at maximum tolerated dose (MTD). Characteristics associated with transfusions were analyzed with univariate and multivariable models. Transfusion incidence rate ratios (IRR) across treatment periods were calculated. Among 635 enrolled children with 4124 person-years of observation, 258 participants (40.4%) received 545 transfusions. The transfusion rate per 100 person-years was 43.2 before hydroxyurea, 21.7 on fixed-dose, 14.5 during dose escalation, and 10.8 on MTD. During MTD, transfusion incidence was reduced by 75% compared to pre-treatment (IRR 0.25, 95% confidence interval [CI] 0.18-0.35, p < .0001), and by 50% compared to fixed dose (IRR 0.50, 95% CI 0.39-0.63, p < .0001). Hydroxyurea at MTD decreases transfusion utilization in African children with SCA. If widely implemented, universal testing and hydroxyurea treatment at MTD could potentially prevent 21% of all pediatric transfusions administered in sub-Saharan Africa. Increasing hydroxyurea access for SCA should decrease the transfusion burden and increase the overall blood supply.
Assuntos
Anemia Falciforme , Hidroxiureia , Criança , Humanos , Hidroxiureia/uso terapêutico , Antidrepanocíticos/uso terapêutico , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Uganda , QuêniaRESUMO
INTRODUCTION: Stroke is a severe complication of sickle cell anemia (SCA), with devastating sequelae. Transcranial Doppler (TCD) ultrasonography predicts stroke risk, but implementing TCD screening with suitable treatment for primary stroke prevention in low-resource environments remains challenging. SPHERE (NCT03948867) is a prospective phase 2 open-label hydroxyurea trial for SCA in Tanzania. METHODS: After formal training and certification, local personnel screened children 2-16 years old; those with conditional (170-199 cm/s) or abnormal (≥200 cm/s) time-averaged mean velocities (TAMVs) received hydroxyurea at 20 mg/kg/day with dose escalation to maximum tolerated dose (MTD). The primary study endpoint is change in TAMV after 12 months of hydroxyurea; secondary endpoints include SCA-related clinical events, splenic volume and function, renal function, infections, hydroxyurea pharmacokinetics, and genetic modifiers. RESULTS: Between April 2019 and April 2020, 202 children (average 6.8 ± 3.5 years, 53% female) enrolled and underwent TCD screening; 196 were deemed eligible by DNA testing. Most had numerous previous hospitalizations and transfusions, with low baseline hemoglobin (7.7 ± 1.1 g/dL) and %HbF (9.3 ± 5.4%). Palpable splenomegaly was present at enrollment in 49 (25%); average sonographic splenic volume was 103 mL (range 8-1,045 mL). TCD screening identified 22% conditional and 2% abnormal velocities, with hydroxyurea treatment initiated in 96% (45/47) eligible children. CONCLUSION: SPHERE has built local capacity with high-quality research infrastructure and TCD screening for SCA in Tanzania. Fully enrolled participants have a high prevalence of elevated baseline TCD velocities and splenomegaly. SPHERE will prospectively determine the benefits of hydroxyurea at MTD for primary stroke prevention, anticipating expanded access to hydroxyurea treatment across Tanzania.
Assuntos
Anemia Falciforme , Acidente Vascular Cerebral , Criança , Humanos , Feminino , Pré-Escolar , Adolescente , Masculino , Hidroxiureia/efeitos adversos , Estudos Prospectivos , Esplenomegalia/complicações , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/epidemiologia , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , África SubsaarianaRESUMO
Hydroxyurea (hydroxycarbamide) is an effective treatment for sickle cell anaemia (SCA), but clinical responses depend primarily upon the degree of fetal haemoglobin (HbF) induction and the heterogeneity of HbF expression across erythrocytes. The number and characteristics of HbF-containing cells (F-cells) are not assessed by traditional HbF measurements. Conventional hydroxyurea dosing (e.g. fixed doses or low starting doses with stepwise escalation) produces a moderate heterocellular HbF induction, but haemolysis and clinical complications continue. Robust, pancellular HbF induction is needed to minimise or fully inhibit polymerisation of sickle haemoglobin. We treated children with hydroxyurea using an individualised, pharmacokinetics-guided regimen starting at predicted maximum tolerated dose (MTD). We observed sustained HbF induction (mean >30%) for up to 6 years, which was not dependent on genetic determinants of HbF expression. Nearly 70% of patients had ≥80% F-cells (near-pancellular), and almost half had ≥90% F-cells (pancellular). The mean HbF/F-cell content was ~12 pg. Earlier age of initiation and better medication adherence were associated with high F-cell responses. In summary, early initiation of hydroxyurea using pharmacokinetics-guided starting doses at predicted MTD can achieve sustained near-pancellular or pancellular HbF expression and should be considered an achievable goal for children with SCA treated with hydroxyurea at optimal doses. Clinical trial registration number: NCT02286154 (clinicaltrials.gov).
Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/uso terapêutico , Hemoglobina Fetal/análise , Hidroxiureia/uso terapêutico , Adolescente , Antidrepanocíticos/administração & dosagem , Antidrepanocíticos/farmacocinética , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Feminino , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/farmacocinética , Masculino , Medicina de PrecisãoRESUMO
We conducted a pilot study to determine the effectiveness of a linkage to care intervention with social workers to improve 12-month post-hospital mortality for children in Tanzania with sickle cell disease. Comparison was done with a historical cohort. Mortality was 6.7% in the interventional cohort compared with 19.2% (adjusted Hazard Ratio, 0.26; 95% CI, 0.08-0.83).
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Anemia Falciforme/mortalidade , Anemia Falciforme/terapia , Continuidade da Assistência ao Paciente/organização & administração , Hospitalização , Melhoria de Qualidade/organização & administração , Serviço Social/organização & administração , Criança , Feminino , Seguimentos , Humanos , Masculino , Projetos Piloto , Melhoria de Qualidade/estatística & dados numéricos , Tanzânia/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Severe anemia is common and frequently fatal for hospitalized patients in limited-resource settings. Lack of access to low-cost, accurate, and rapid diagnosis of anemia impedes the delivery of life-saving care and appropriate use of the limited blood supply. The WHO Haemoglobin Colour Scale (HCS) is a simple low-cost test but frequently inaccurate. AnemoCheck-LRS (limited-resource settings) is a rapid, inexpensive, color-based point-of-care (POC) test optimized to diagnose severe anemia. METHODS: Deidentified whole blood samples were diluted with plasma to create variable hemoglobin (Hb) concentrations, with most in the severe (≤ 7 g/dL) or profound (≤ 5 g/dL) anemia range. Each sample was tested with AnemoCheck-LRS and WHO HCS independently by three readers and compared to Hb measured by an electronic POC test (HemoCue 201+) and commercial hematology analyzer. RESULTS: For 570 evaluations within the limits of detection of AnemoCheck-LRS (Hb ≤ 8 g/dL), the average difference between AnemoCheck-LRS and measured Hb was 0.5 ± 0.4 g/dL. In contrast, the WHO HCS overestimated Hb with an absolute difference of 4.9 ± 1.3 g/dL for samples within its detection range (Hb 4-14 g/dL, n = 405). AnemoCheck-LRS was much more sensitive (92%) for the diagnosis of profound anemia than WHO HCS (22%). CONCLUSIONS: AnemoCheck-LRS is a rapid, inexpensive, and accurate POC test for anemia. AnemoCheck-LRS is more accurate than WHO HCS for detection of low Hb levels, severe anemia that may require blood transfusion. AnemoCheck-LRS should be tested prospectively in limited-resource settings where severe anemia is common, to determine its utility as a screening tool to identify patients who may require transfusion.
Assuntos
Anemia/diagnóstico , Saúde Global/normas , Recursos em Saúde/normas , Testes Imediatos/normas , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: To determine the regional- and district-level newborn prevalence of sickle cell trait and disease, and the prevalence of haemoglobin variants and genetic modifiers of sickle cell disease, in the nine regions of north-western United Republic of Tanzania. METHODS: We repurposed dried blood spot samples from children (aged 0-24 months) born to mothers living with human immunodeficiency virus (HIV), collected as part of the HIV Early Infant Diagnosis programme, for sickle cell diagnosis. We performed isoelectric focusing to determine whether samples had normal haemoglobin, sickle cell trait, sickle cell disease or a rare haemoglobin variant. We shipped samples diagnosed as disease or variant to Cincinnati Children's Hospital in the United States of America for deoxyribonucleic-acid-based analyses to determine the prevalence of α-thalassaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency or fetal haemoglobin genetic modifiers. FINDINGS: We analysed a total of 17 200 specimens during February 2017-May 2018. We observed a prevalence of sickle cell trait and disease of 20.3% (3492/17 200) and 1.2% (210/17 200), respectively. District-level trait varied from 8.6% (5/58) to 28.1% (77/274). Among confirmed sickle cell disease specimens, we noted 42.7% (61/143) had 1-gene deletion and 14.7% (21/143) had 2-gene deletion α-thalassaemia trait. We documented G6PD A- deficiency in 19.2% (14/73) of males. CONCLUSION: Our calculated prevalence is twice as high as previously reported and reinforces the need for enhanced sickle cell diagnostic services. Our district-level data will inform public health policy, allowing screening and disease-modifying hydroxyurea therapy to be focused on high-prevalence areas, until universal newborn screening is available.
Assuntos
Anemia Falciforme , Deficiência de Glucosefosfato Desidrogenase , Traço Falciforme , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Anemia Falciforme/genética , Humanos , Recém-Nascido , Masculino , Triagem Neonatal , Prevalência , Traço Falciforme/diagnóstico , Traço Falciforme/epidemiologia , Traço Falciforme/genética , Tanzânia/epidemiologiaRESUMO
BACKGROUND/OBJECTIVES: Sickle cell disease (SCD) is an important, hidden cause of childhood mortality worldwide. It is most prevalent in sub-Saharan Africa where national newborn screening programs remain unavailable and most children in rural areas are never diagnosed. We conducted a study at a rural district hospital in northern Tanzania to determine the birth prevalence and community awareness of SCD and to determine the feasibility of using point-of-care testing to enroll newborns in a new SCD clinic for ongoing treatment. DESIGN/METHODS: We screened infants at Shirati KMT hospital for SCD using HemoTypeSC, an inexpensive point-of-care test. Infants who screened positive were enrolled in the SCD clinic and instructed to return at 6-12 weeks for confirmatory testing, counseling, and preventive care. RESULTS: A total of 999 newborns were screened from February to September 2019. Among these, 31.6% (315/999) had sickle cell trait and 3.9% (39/999) had SCD. No hemoglobin C was detected. Very few parents knew their own sickle cell status (0.3%). At 5 months after completion, 12 infants from the screening study and 30 additional children had been seen at the SCD clinic for ongoing counseling and care. CONCLUSIONS: Birth prevalence of SCD in rural Tanzania is extremely high and community awareness is low. Newborn point-of-care testing enhances case finding and enables early enrollment in preventive care for SCD, even in rural sub-Saharan Africa with minimal laboratory capacity. SCD-specific clinical services implemented at the district hospital level could expand access to many children and significantly reduce early SCD morbidity and mortality.
Assuntos
Anemia Falciforme/epidemiologia , Triagem Neonatal/métodos , População Rural/estatística & dados numéricos , Traço Falciforme/epidemiologia , Anemia Falciforme/diagnóstico , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , Prevalência , Prognóstico , Estudos Prospectivos , Traço Falciforme/diagnóstico , Tanzânia/epidemiologiaRESUMO
Both anemia and sickle cell disease (SCD) are highly prevalent across sub-Saharan Africa, and limited resources exist to diagnose these conditions quickly and accurately. The development of simple, inexpensive, and accurate point-of-care (POC) assays represents an important advance for global hematology, one that could facilitate timely and life-saving medical interventions. In this prospective study, Robust Assays for Point-of-care Identification of Disease (RAPID), we simultaneously evaluated a POC immunoassay (Sickle SCAN™) to diagnose SCD and a first-generation POC color-based assay to detect anemia. Performed at Bugando Medical Center in Mwanza, Tanzania, RAPID tested 752 participants (age 1 day to 20 years) in four busy clinical locations. With minimally trained medical staff, the SCD POC assay diagnosed SCD with 98.1% sensitivity and 91.1% specificity. The hemoglobin POC assay had 83.2% sensitivity and 74.5% specificity for detection of severe anemia (Hb ≤ 7 g/dL). Interobserver agreement was excellent for both POC assays (r = 0.95-0.96). Results for the hemoglobin POC assay have informed the second-generation assay design to be more suitable for low-resource settings. RAPID provides practical feasibility data regarding two novel POC assays for the diagnosis of anemia and SCD in real-world field evaluations and documents the utility and potential impact of these POC assays for sub-Saharan Africa.
Assuntos
Anemia Falciforme/diagnóstico , Anemia/diagnóstico , Colorimetria/métodos , Hemoglobinas/metabolismo , Testes Imediatos , Adolescente , Anemia/sangue , Anemia Falciforme/sangue , Criança , Pré-Escolar , Colorimetria/economia , Feminino , Humanos , Imunoensaio , Lactente , Recém-Nascido , Masculino , Variações Dependentes do Observador , Estudos Prospectivos , Sensibilidade e Especificidade , Tanzânia , Adulto JovemRESUMO
BACKGROUND: Worldwide, hemoglobinopathies affect millions of children. Identification of hemoglobin disorders in most sub-Saharan African countries is delayed until clinical signs of the disease are present. Limited studies have been conducted to understand their prevalence and clinical presentation among newborns in resource-limited settings. METHODOLOGY: This was a prospective cohort study. Newborns (aged 0-7 days) at two hospitals in Northwestern Tanzania were enrolled and followed prospectively for 6 months. Clinical and laboratory information were collected at baseline. Participants were screened for hemoglobinopathies using high-performance liquid chromatography. Clinical and laboratory follow-up was performed at 3 and 6 months for those with hemoglobinopathies as well as a comparison group of participants without hemoglobinopathies. RESULTS: A total of 919 newborns were enrolled. Among these, 1.4% (13/919) had sickle cell anemia or Hb S/ß0 -thalassemia (Hb FS), and 19.7% (181/919) had sickle cell trait or Hb S/ß+ thalassemia (Hb FAS). Furthermore, 0.2% (two of 919) had ß+ -thalassemia. Red cell indices compared between Hb FS, Hb FAS, and Hb FA were similar at baseline, but hemoglobin was lower and red cell distribution width was higher in children with Hb FS at 3- and 6-month follow-up. Febrile episodes were more common for children with Hb FS at 3- and 6-month follow-up. CONCLUSION: The prevalence of sickle cell disease among neonates born in Northwestern Tanzania is one of the highest in the world. Newborn screening is needed early in life to identify neonates with hemoglobinopathies so that clinical management may commence and morbidity and mortality related to hemoglobinopathies be reduced.
Assuntos
Anemia Falciforme/epidemiologia , Doenças do Recém-Nascido/epidemiologia , Adulto , Anemia Falciforme/sangue , Feminino , Seguimentos , Humanos , Recém-Nascido , Doenças do Recém-Nascido/sangue , Masculino , Prevalência , Estudos Prospectivos , Tanzânia/epidemiologiaRESUMO
BACKGROUND: Worldwide Helicobacter pylori (H.pylori) treatment is of great challenge due to increased antibiotic resistance. The burden of H. pylori antibiotic resistance in Africa is high with unclear information regarding the real magnitude. This systematic review and meta-analysis was conducted to investigate the magnitude of H.pylori antibiotic resistance in Africa to gain insight of the extent of the problem among H.pylori naïve treatment patients. METHOD: The search was performed in the academic databases, Embase, PubMed, Web of Science and Africa Wide Information. ProQuest Dissertation and Theses, Scopus, Ethos, Africa Index Medicus (WHO), BioMed Central Proceedings, BASE, British Library, Open grey, Library of Congress and the New York Academy of Grey Literature Report were additionally searched for grey literature. Published articles from Africa on H.pylori antibiotic resistance between 1986 and June 2017 were systematically reviewed to estimate the H. pylori extent of resistance to macrolides, quinolones, amoxicillin, tetracycline and metronidazole. RESULTS: In 26 articles a total of 2085 isolates were tested for metronidazole, 1530 for amoxicillin, 1277 for tetracycline, 1752 for clarithromycin and 823 for quinolones.The overall pooled proportion of H.pylori resistance to quinolones, clarithromycin, tetracycline, metronidazole and amoxicillin were: (17.4%, 95%CI 12.8 - 21.9), (29.2%, 95%CI:26.7-31.8), (48.7%, 95%CI: 44.5-52.9), (75.8%, 95% CI: 74.1-.77.4) and (72.6%, 95% CI: 68.6-76.6), respectively. The commonest mutation detected were A2143G (49/97) for clarithromycin, RdxA (41/56) for metronidazole and D87I (16/40) for quinolones. CONCLUSION: Prevalence of metronidazole, clarithromycin, and amoxicillin resistance is high in developing world including Africa. This could impair the first line triple therapy of the H.pylori infection. There is a need of conducting surveillance of H.pylori susceptibility pattern in Africa for dual and triple resistance which can be used for the empirical treatment.
Assuntos
Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Mutação , África , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , PrevalênciaRESUMO
Parvovirus B19 (B19) can cause transient aplastic crisis and lead to acute severe anemia. This study investigated the relationship between B19 and anemia among children <5 years old in the city of Mwanza, Tanzania. An enzyme immunoassay was used to detect B19 IgM- and IgG-specific antibodies among children with various categories of anemia according to the World Health Organization (WHO) guidelines. A total of 265 children with median age of 28.5 months (interquartile range 18-39.5) were investigated. Eighty-six children (32.5%) had severe anemia. B19-specific IgM and IgG antibodies were detected in 24 (9%) and 46 (17.4%) children, respectively. Low hemoglobin (Hb) level (p = 0.031), Plasmodium falciparum infection (p = 0.001) and residing in rural areas (p = 0.025) independently predicted B19 IgM seropositivity. Acute B19 infection decreased Hb level by 1.1 g/dl (p = 0.003). In malaria endemic areas, acute B19 infections should be considered among children with severe anemia from rural areas.
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Anemia/complicações , Anemia/virologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Infecções por Parvoviridae/complicações , Parvovirus B19 Humano/imunologia , Parvovirus B19 Humano/isolamento & purificação , Anemia Aplástica/epidemiologia , Anemia Aplástica/virologia , Anticorpos Antivirais/sangue , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Técnicas Imunoenzimáticas , Lactente , Recém-Nascido , Masculino , Infecções por Parvoviridae/imunologia , Reação em Cadeia da Polimerase , TanzâniaRESUMO
The global burden of kidney disease is increasing, and several etiologies first begin in childhood. Risk factors for pediatric kidney disease are common in Africa, but data regarding its prevalence are lacking. We completed a systematic review of community-based studies describing the prevalence of proteinuria, hematuria, abnormal imaging, or kidney dysfunction among children in sub-Saharan Africa (SSA). Medline and Embase were searched. Five hundred twenty-three references were reviewed. Thirty-two references from nine countries in SSA were included in the qualitative synthesis. The degree of kidney damage and abnormal imaging varied widely: proteinuria 32.5% (2.2-56.0%), hematuria 31.1% (0.6-67.0%), hydronephrosis 11.3% (0.0-38.0%), hydroureter 7.5% (0.0-26.4%), and major kidney abnormalities 0.1% (0.0-0.8%). Serum creatinine was reported in four studies with insufficient detail to identify the prevalence renal dysfunction. A majority of the studies were performed in Schistosoma haematobium endemic areas. A lower prevalence of kidney disease was observed in the few studies from nonendemic areas. Published data on pediatric kidney disease in SSA are highly variable and dependent on S. haematobium prevalence. More community-based studies are needed to describe the burden of pediatric kidney disease, particularly in regions where S. haematobium infection is nonendemic.
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Nefropatias/epidemiologia , Nefropatias/etiologia , Nefropatias/patologia , Esquistossomose Urinária/epidemiologia , África Subsaariana/epidemiologia , Criança , Creatinina/sangue , Hematúria/epidemiologia , Humanos , Prevalência , Proteinúria/epidemiologia , Fatores de Risco , Esquistossomose Urinária/complicaçõesRESUMO
Hypertension is increasingly common in sub-Saharan Africa, and rates of hypertension control are low. Use of traditional herbal medicines (THM) is common among adults in sub-Saharan Africa and may affect hypertension therapy. We searched Ovid MEDLINE, Ovid EMBASE, and Web of Knowledge in June 2013 to find studies about THM use among hypertensive patients living in sub-Saharan Africa. Two independent reviewers evaluated titles and abstracts. Qualifying references were reviewed in full text. Data were extracted using a standardized questionnaire. Four hundred and eighty-one references were retrieved, and four articles from two countries met criteria for inclusion. The prevalence of THM use was 25-65% (average 38.6%). THM was the most common type of complementary and alternative medicines used by patients (86.7-96.6%). Among THM users, 47.5% concomitantly used both allopathic medicine and THM. Increased age (p<0.001), male sex (RR 2.58), belief in a supernatural cause of hypertension (RR 2.11), and family history of hypertension (OR 1.78) were positively associated with THM use, while belief that hypertension is preventable was negatively associated with THM use (OR 0.57). More than one-third of adults with hypertension in sub-Saharan Africa use THM. Half of these patients use THM concurrently with allopathic medicine. Healthcare workers in sub-Saharan Africa must discuss THM use with their hypertensive patients. More research is urgently needed to define the impact of THM use on hypertension control and outcomes in sub-Saharan Africa.
Assuntos
Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Fitoterapia/métodos , Adulto , África Subsaariana , Idoso , Determinação da Pressão Arterial , Países em Desenvolvimento , Feminino , Medicina Herbária/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common cause of hospital admissions worldwide. Aetiologies vary by sociodemographics and geography. Retrospective studies of endoscopies in much of Africa have documented oesophageal varices as a leading cause of UGIB. Prospective studies describing outcomes and associations with clinical factors are lacking. METHODS: We conducted a prospective cohort study at a referral hospital in Mwanza, Tanzania where schistosomiasis is endemic. Adults admitted with haematemesis underwent laboratory workup, schistosomiasis antigen testing and elective endoscopy, and were followed for two months for death or re-bleeding. We assessed predictors of endoscopic findings using logistic regression models, and determined prediction rules that maximised sensitivity and positive predictive value (PPV). RESULTS: Of 124 enrolled patients, 13 died within two months (10%); active schistosomiasis prevalence was 48%. 64/91(70%) patients had oesophageal varices. We found strong associations between varices and numerous demographic or clinical findings, permitting construction of simple, high-fidelity prediction rules for oesophageal varices applicable even in rural settings. Portal vein diameter ≥ 13 mm or water sourced from the lake yielded sensitivity, specificity, PPV and NPV >90% for oesophageal varices; presence of splenomegaly or water sourced from the lake maintained sensitivity and PPV >90%. CONCLUSIONS: Our results guide identification of patients, via ultrasound and clinical examination, likely to have varices for whom referral for endoscopy may be life-saving. Furthermore, they support empiric anti-schistosome treatment for patients with UGIB in schistosome-endemic regions. These interventions have potential to reduce UGIB-related morbidity and mortality in Africa.
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Varizes Esofágicas e Gástricas/epidemiologia , Hemorragia Gastrointestinal/epidemiologia , Esquistossomose/epidemiologia , Adulto , Estudos de Coortes , Varizes Esofágicas e Gástricas/complicações , Feminino , Hemorragia Gastrointestinal/complicações , Hemorragia Gastrointestinal/mortalidade , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Esquistossomose/complicações , Esquistossomose/mortalidade , Tanzânia/epidemiologiaRESUMO
BACKGROUND: Despite the increased availability of anti-retroviral therapy, in-hospital HIV mortality remains high in sub-Saharan Africa. Reports from Senegal, Malawi, and Tanzania show rates of in-hospital, HIV-related mortality ranging from 24.2% to 44%. This mixed methods review explored the potential causes of preventable in-hospital mortality associated with HIV infections in sub-Saharan Africa in the anti-retroviral era. RESULTS: Based on our experience as healthcare providers in Africa and a review of the literature we identified 5 health systems failures which may cause preventable in-hospital mortality, including: 1) late presentation of HIV cases, 2) low rates of in-hospital HIV testing, 3) poor laboratory capacity which limits CD4 T-cell testing and the diagnosis of opportunistic infections, 4) delay in initiation of anti-retroviral therapy in-hospital, and 5) problems associated with loss to follow-up upon discharge from hospital. CONCLUSION: Our findings, together with the current available literature, should be used to develop practical interventions that can be implemented to reduce in-hospital mortality.
Assuntos
Infecções por HIV/mortalidade , Mortalidade Hospitalar , Pacientes Internados , Adulto , África Subsaariana , Linfócitos T CD4-Positivos , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Realizing Effectiveness Across Continents with Hydroxyurea (REACH) is an open-label non-randomised trial of hydroxyurea (hydroxycarbamide) in children with sickle cell anaemia in sub-Saharan Africa. The short-term results of REACH on safety, feasibility, and effectiveness of hydroxyurea were published previously. In this paper we report results from extended hydroxyurea treatment in the REACH cohort up to 8 years. METHODS: In this open-label, non-randomised, phase 1/2 trial, participants were recruited from four clinical sites in Kilifi, Kenya; Mbale, Uganda; Luanda, Angola; and Kinshasa, Democratic Republic of Congo. Eligible children were 1-10 years old with documented haemoglobin SS or haemoglobin Sß zero thalassaemia, weighing at least 10 kg. Participants received fixed-dose hydroxyurea of 17.5 (±2.5) mg/kg per day for 6 months (fixed-dose phase), followed by 6 months of dose escalation (2·5-5·0 mg/kg increments every 8 weeks) as tolerated, up to 20-35 mg/kg per day (maximum tolerated dose; MTD), defined as mild myelosuppression. After the MTD was reached, hydroxyurea dosing was optimised for each participant on the basis of changes in bodyweight and laboratory values over time (MTD with optimisation phase). After completion of the first 12 months, children with an acceptable toxicity profile and favourable responses were given the opportunity to continue hydroxyurea until the age of 18 years. The safety and feasibility results after 3 years has been reported previously. Here, haematological responses, clinical events, and toxicity rates were compared across the dosing phases (fixed-dose hydroxyurea vs MTD with optimisation phase) as protocol-specified outcomes. REACH is registered on ClinicalTrials.gov (NCT01966731) and is ongoing. FINDINGS: We enrolled 635 children between July 4, 2014, and Nov 11, 2016. 606 children were given hydroxyurea and 522 (86%; 266 [51%] boys and 256 [49%] girls) received treatment for a median of 93 months (IQR 84-97) with 4340 patient-years of treatment. The current (Oct 5, 2023) mean dose is 28·2 (SD 5·2) mg/kg per day with an increased mean haemoglobin concentration (7·3 [SD 1·1] g/dL at baseline to 8·5 [1·5] g/dL) and mean fetal haemoglobin level (10·9% [SD 6·8] to 23·3% [9·5]) and decreased absolute neutrophil count (6·8 [3·0] × 109 cells per L to 3·6 [2·2] × 109 cells per L). Incidence rate ratios (IRR) comparing MTD with fixed-dose hydroxyurea indicate decreased vaso-occlusive episodes (0·60; 95% CI 0·52-0·70; p<0·0001), acute chest syndrome events (0·21; 0·13-0·33; p<0·0001), recurrent stroke events (0·27; 0·07-1·06; p=0·061), malaria infections (0·58; 0·46-0·72; p<0·0001), non-malarial infections (0·52; 0·46-0·58; p<0·0001), serious adverse events (0·42; 0·27-0·67; p<0·0001), and death (0·70; 0·25-1·97; p=0·50). Dose-limiting toxicity rates were similar between the fixed-dose (24·1 per 100 patient-years) and MTD phases (23·2 per 100 patient-years; 0·97; 0·70-1·35; p=0·86). Grade 3 and 4 adverse events were infrequent (18·5 per 100 patient-years) and included malaria infection, non-malarial infections, vaso-occlusive pain, and acute chest syndrome. Serious adverse events were uncommon (3·6 per 100 patient-years) and included malaria infections, parvovirus-associated anaemia, sepsis, and stroke, with no treatment-related deaths. INTERPRETATION: Hydroxyurea dose escalation to MTD with dose optimisation significantly improved clinical responses and treatment outcomes, without increasing toxicities in children with sickle cell anaemia in sub-Saharan Africa. FUNDING: US National Heart, Lung, and Blood Institute and Cincinnati Children's Research Foundation.
Assuntos
Anemia Falciforme , Antidrepanocíticos , Hidroxiureia , Humanos , Hidroxiureia/uso terapêutico , Hidroxiureia/administração & dosagem , Hidroxiureia/efeitos adversos , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/complicações , Anemia Falciforme/sangue , Pré-Escolar , Criança , Masculino , Feminino , África Subsaariana , Seguimentos , Lactente , Antidrepanocíticos/uso terapêutico , Antidrepanocíticos/efeitos adversos , Antidrepanocíticos/administração & dosagem , Resultado do Tratamento , Relação Dose-Resposta a DrogaRESUMO
BACKGROUND: The number of adults with diabetes mellitus is increasing worldwide, particularly in Asia and Africa. In sub-Saharan Africa, renal complications of diabetes may go unrecognized due to limited diagnostic resources. The prevalence of chronic kidney disease (CKD) among adult diabetics in sub-Saharan Africa has not been well described. METHODS: This study was conducted at the diabetes mellitus clinic of Bugando Medical Centre in Mwanza, Tanzania. A total 369 consecutive adult diabetic patients were enrolled and interviewed. Each patient provided a urine sample for microalbuminuria and proteinuria and a blood sample for serum creatinine level. Estimated glomerular filtration rate (eGFR) was calculated using the Cockroft-Gault equation. CKD was staged according to the Kidney Disease Improving Global Outcomes system. RESULTS: A total of 309 (83.7%) study participants had CKD; 295 (80.0%) had significant albuminuria and 91 (24.7%) had eGFR < 60 ml/min. None of these patients were aware of their renal disease, and only 5 (1.3%) had a diagnosis of diabetic nephropathy recorded in their file. Older age was significantly associated with CKD in this population [OR 1.03, p = 0.03, 95%CI (1.00-1.05)]. CONCLUSIONS: Chronic kidney disease is highly prevalent among adult diabetic outpatients attending our clinic in Tanzania, but is usually undiagnosed. Nearly » of patients had an eGFR low enough to require dose adjustment of diabetic medications. More diagnostic resources are needed for CKD screening among adults in Tanzania in order to slow progression and prevent complications.