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BACKGROUND: The true burden of COVID-19 in low- and middle-income countries remains poorly characterized, especially in Africa. Even prior to the availability of SARS-CoV-2 vaccines, countries in Africa had lower numbers of reported COVID-19 related hospitalizations and deaths than other regions globally. METHODS: Ugandan blood donors were evaluated between October 2019 and April 2022 for IgG antibodies to SARS-CoV-2 nucleocapsid (N), spike (S), and five variants of the S protein using multiplexed electrochemiluminescence immunoassays (MesoScale Diagnostics, Rockville, MD). Seropositivity for N and S was assigned using manufacturer-provided cutoffs and trends in seroprevalence were estimated by quarter. Statistically significant associations between N and S antibody seropositivity and donor characteristics in November-December 2021 were assessed by chi-square tests. RESULTS: A total of 5393 blood unit samples from donors were evaluated. N and S seropositivity increased throughout the pandemic to 82.6% in January-April 2022. Among seropositive individuals, N and S antibody levels increased ≥9-fold over the study period. In November-December 2021, seropositivity to N and S antibody was higher among repeat donors (61.3%) compared with new donors (55.1%; p = .043) and among donors from Kampala (capital city of Uganda) compared with rural regions (p = .007). Seropositivity to S antibody was significantly lower among HIV-seropositive individuals (58.8% vs. 84.9%; p = .009). CONCLUSIONS: Despite previously reported low numbers of COVID-19 cases and related deaths in Uganda, high SARS-CoV-2 seroprevalence and increasing antibody levels among blood donors indicated that the country experienced high levels of infection over the course of the pandemic.
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Doadores de Sangue , COVID-19 , Humanos , Uganda/epidemiologia , SARS-CoV-2 , Vacinas contra COVID-19 , Estudos Soroepidemiológicos , COVID-19/epidemiologia , Anticorpos AntiviraisRESUMO
BACKGROUND: Viral load (VL) testing is key in monitoring adherence to antiretroviral therapy (ART) and documenting HIV treatment response. As per HIV treatment guidelines in Uganda, the first VL test is recommended 6 months after initiation of ART. Undetectable VL (uVL) at ART initiation may be helpful in detecting elite controllers in the absence of previous ART use. We investigated viral suppression at ART initiation among a cohort of HIV-positive pregnant women enrolled in the Friends for Life Circles (FLC) for Option B+ randomized controlled trial (RCT). METHODS: Pregnant women ≥ 18 years of age testing positive for HIV at their first antenatal care visit and starting on ART Option B+ as per the National PMTCT Program guidelines were enrolled into the FLC for Option B+ RCT in urban Kampala and rural Mityana districts of Uganda. Each participant had whole blood samples collected at enrolment to assess baseline VL. Plasma HIV-1 RNA was quantified using COBAS Ampliprep /COBAS Taqman. Baseline VL below 400 RNA copies/ml was considered as viral suppression while baseline VL below 20 RNA copies/ml was considered uVL. RESULTS: The mean duration from the date of ART initiation to time of sample collection for baseline VL assessment was 4.4 days (SD 3.6). Of the 532 HIV-positive pregnant women enrolled in the FLC for Option B+ study and newly starting Option B+ without a self-reported history of prior ART use, 29 (5.5%) had uVL and 113 (21.4%) had suppressed VL at baseline. There was no association between participants' age, gravidity, marital status, mean monthly income, educational level, disclosure of HIV status to partner, and uVL or viral suppression at baseline. However, non-disclosure of HIV status to any other person was associated with decreased odds of viral suppression at baseline (OR 0.640; 0.416-0.982). CONCLUSION: Twenty-one percent of HIV-positive Ugandan pregnant women initiating ART (Option B+) showed virological suppression at baseline and were presumed to be "elite controllers" or to have misreported being ART-naive. Further studies are needed to better understand the biologic mechanisms of elite controllers among pregnant women as well as to differentiate elite controllers from concealed ART use. Trial Registration The trial was registered as NCT02515370 (04/08/2015) on Clinicaltrials.gov.
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Fármacos Anti-HIV , Infecções por HIV , Complicações Infecciosas na Gravidez , Fármacos Anti-HIV/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Gestantes , Prevalência , Uganda/epidemiologia , Carga ViralRESUMO
BACKGROUND: Malaria remains a leading transfusion associated infectious risk in endemic areas. However, the prevalence of malaria parasitemia has not been well characterized in blood donor populations. This study sought to determine the prevalence of Plasmodium in red blood cell (RBC) and whole blood (WB) units after the rainy season in Uganda. METHODS AND MATERIALS: Between May and July 2018, blood was collected from the sample diversion pouch of 1000 WB donors in Kampala and Jinja, Uganda. The RBC pellet from ethylenediamine tetraacetic acid (EDTA) anticoagulated blood was stored at -80°C until testing. DNA was extracted and nested PCR was used to screen samples at the genus level for Plasmodium, with positive samples further tested for species identification. RESULTS: Malaria parasitemia among asymptomatic, eligible blood donors in two regions of Uganda was 15.4%; 87.7% (135/154) of infections were with P. falciparum, while P. malariae and P. ovale were also detected. There were 4.3% of blood donors who had mixed infection with multiple species. Older donors (>30 years vs. 17-19 years; aPR = 0.31 [95% CI = 0.17-0.58]), females (aPR = 0.60 [95% CI = 0.42-0.87]), repeat donors (aPR = 0.44 [95% CI = 0.27-0.72]) and those donating near the capital city of Kampala versus rural Jinja region (aPR = 0.49 [95% CI = 0.34-0.69]) had a lower prevalence of malaria parasitemia. CONCLUSIONS: A high proportion of asymptomatic blood donors residing in a malaria endemic region demonstrate evidence of parasitemia at time of donation. Further research is needed to quantify the risk and associated burden of transfusion-transmitted malaria (TTM) in order to inform strategies to prevent TTM.
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Doadores de Sangue/estatística & dados numéricos , Malária/epidemiologia , Parasitemia/epidemiologia , Adolescente , Adulto , Infecções Assintomáticas/epidemiologia , Transfusão de Sangue/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Malária/sangue , Malária Falciparum/sangue , Malária Falciparum/epidemiologia , Masculino , Pessoa de Meia-Idade , Parasitemia/sangue , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/isolamento & purificação , Plasmodium malariae/crescimento & desenvolvimento , Plasmodium malariae/isolamento & purificação , Plasmodium ovale/crescimento & desenvolvimento , Plasmodium ovale/isolamento & purificação , Prevalência , Uganda/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The global tuberculosis (TB) estimate in 2011 was 500,000 cases among children under 15 years representing 5.7 % of all cases and 64, 000 deaths among HIV negative children representing 6.5 % of the total deaths. In Uganda, the child TB cases reported in 2012 made up less than 3 % of the total cases while recent modelling estimates it at 15-20 % of adult cases. Mapping of these cases in Kampala district most especially for the children under five years would reflect recent transmission in the various communities in the district. We therefore conducted a retrospective study of reported child TB cases in Kampala district Uganda for 2009-2010 to provide an estimate of child TB incidence and map the cases. METHODS: This was a retrospective cross-sectional study on data collected from the health unit TB registers in the five divisions of Kampala district, Uganda. The data was a starting point in preparation for a TB Vaccine study in children. The extracted data spanned a period from 1st January 2009 to 31st December 2010. The projected population of children below 15 years was 637,922 in 2009 and 744,750 in 2010 for Kampala district. We based our projections on the National Bureau of Statistics most recent census report of 2002 before the study duration while assuming a population growth rate of 3.7 % each year. We captured the data into EPI DATA 3.1 and analysed it using STATA version 12. RESULTS: We accessed 15,499 records and analysed 1167 records that were of children below 15 years old. The child TB cases represented 7.5 % (7.3 in 2009 & 7.6 % in 2010) of all the registered cases in Kampala district. The females were 47 % and the median age was 4 years (IQR 1, 10). The percent of children less than 5 years old was 54 %. The percent of pulmonary TB cases was 89 % (1041/1167) with 15 % smear positive. The proportion of extra-pulmonary TB cases was 11 % (126/1167). Among those that tested for HIV, 60 % (359/620) had test results available with an HIV co-infection rate of 47 % (168/359). Antiretroviral treatment uptake was 24 % among the co-infected. The incidence of child TB in Kampala was 56 (95 % CI 50-62) per 100,000 in 2009 and 44 (95 % CI 40-49) per 100,000 in 2010. Most of the TB cases (60 % (410/685)) in Kampala live in slum areas. CONCLUSION: There was a higher child TB incidence of 56 per 100,000 in 2009 compared with 44 per 100,000 in 2010. The percentage of child TB cases was much higher at 7.5 % of all the reported TB cases than the WHO reported national average. For the review period, the TB cases clustered in particular slums in Kampala district.
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Tuberculose/epidemiologia , Adolescente , Criança , Pré-Escolar , Coinfecção/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Incidência , Lactente , Masculino , Áreas de Pobreza , Estudos Retrospectivos , Tuberculose Pulmonar/epidemiologia , Uganda/epidemiologiaRESUMO
Objectives: Blood transfusion is an important mode of infectious disease transmission in low- and middle-income countries (LMICs). This study describes a model to determine the prevalence of transfusion-transmitted infections (TTIs) and the associated burden of disease. Methods: A five-step model was developed to determine the TTI-related burden of disease measured by disability-adjusted life years (DALYs). Uganda was selected as the study country. Results: Approximately 298,266 units of blood were transfused in Uganda in 2019, yielding an estimated TTI incidence of 6,858 new TTIs (2.3% of transfused units) and prevalence of 19,141 TTIs (6.4% of transfused units). The total burden of disease is 2,903 DALYs, consisting of approximately 2,590 years of life lost (YLLs), and 313 years lived with disability (YLDs). Conclusion: The incidence and prevalence of TTIs and the associated burden of disease can be calculated on a local and national level. The model can be applied by health ministries to estimate the impact of TTIs in order to develop blood safety strategies to reduce the burden of disease.
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Efeitos Psicossociais da Doença , Anos de Vida Ajustados por Deficiência , Reação Transfusional , Humanos , Uganda/epidemiologia , Incidência , Reação Transfusional/epidemiologia , Prevalência , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Infecções Transmitidas por Sangue/epidemiologia , Criança , Adulto Jovem , Pré-Escolar , Lactente , Anos de Vida Ajustados por Qualidade de VidaRESUMO
INTRODUCTION: Despite the scale-up of Option B+, long-term retention of women in HIV care during pregnancy and the postpartum period remains an important challenge. We compared adherence to clinic appointments and antiretroviral therapy (ART) at 6 weeks, 6, and and 24 months postpartum among pregnant women living with HIV and initiating Option B+. Women were randomized to a peer group support, community-based drug distribution and income-generating intervention called "Friends for Life Circles" (FLCs) versus the standard of care (SOC). Our secondary outcome was infant HIV status and HIV-free survival at 6 weeks and 18 months postpartum. METHODS: Between 16 May 2016 and 12 September 2017, 540 ART-naïve pregnant women living with HIV at urban and rural health facilities in Uganda were enrolled in the study at any gestational age. Participants were randomized 1:1 to the unblinded FLC intervention or SOC at enrolment and assessed for adherence to the prevention of mother-to-child HIV transmission (PMTCT) clinic appointments at 6 weeks, 12, and 24 months postpartum, self-reported adherence to ART at 6 weeks, 6 and 24 months postpartum and supported by plasma HIV-1 RNA viral load (VL) measured at the same time points, retention in care through the end of study, and HIV status and HIV-free survival of infants at 18 months postpartum. The FLC groups were formed during pregnancy within 4 months of enrollment and held monthly meetings in their communites, and were followed up until the last group participant reached 24 months post delivery. We used Log-rank and Chi-Square p-values to test the equality of Kaplan-Meier survival probabilities and hazard rates (HR) for failure to retain in care for any reason by study arm. RESULTS: There was no significant difference in adherence to PMTCT clinic visits or to ART or in median viral loads between FLC and SOC arms at any follow-up time points. Retention in care through the end of study was high in both arms but significantly higher among participants randomized to FLC (86.7%) compared to SOC (79.3%), p = 0.022. The adjusted HR of visit dropout was 2.4 times greater among participants randomized to SOC compared to FLC (aHR = 2.363, 95% CI: 1.199-4.656, p = 0.013). Median VL remained < 400 copies/ml in both arms at 6 weeks, 6, and 24 months postpartum. Eight of the 431 infants tested at 18 months were HIV positive (1.9%), however, this was not statistically different among mothers enrolled in the FLC arm compared to those in the SOC arm. At 18 months, HIV-free survival of children born to mothers in the FLC arm was significantly higher than that of children born to mothers in the SOC arm. CONCLUSIONS: Our findings suggest that programmatic interventions that provide group support, community-based ART distribution, and income-generation activities may contribute to retention in PMTCT care, HIV-free survival of children born to women living with HIV, and ultimately, to the elimination of mother-to-child HIV transmission (EMTCT). TRIAL REGISTRATION: NCT02515370 (04/08/2015) on ClinicalTrials.gov.
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Fármacos Anti-HIV , Infecções por HIV , Complicações Infecciosas na Gravidez , Retenção nos Cuidados , Lactente , Humanos , Feminino , Gravidez , HIV , Mães , Uganda , Fármacos Anti-HIV/uso terapêutico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/prevenção & controle , Grupo AssociadoRESUMO
BACKGROUND: In 2016, the World Health Organization recommended that a fractional dose of yellow fever (YF) vaccine could be used in persons 2 years of age or older in response to an emergency that resulted in a global shortage of available YF vaccine. However, this recommendation did not extend to the youngest age group licensed for YF vaccine because there were no published data on the use or safety of fractional dose YF vaccination in children aged 9-23 months. We conducted a single-blind randomized controlled trial, comparing the immunogenicity and safety of fractional one-fifth and one-half doses of Bio-Manguinhos 17DD YF vaccine with full dose in children aged 9-23 months old in Uganda. In this paper, we present the interim analysis on safety. METHODS: Children aged 9-23 months presenting for routine well-child services were recruited for inclusion at one of three study sites. We collected data during March 26, 2019-August 31, 2020, on all adverse events following immunization (AEFI) during active surveillance for 28 days post-vaccination using multiple collection tools including a diary card with an objective measurement of fever. An independent team from the Uganda national AEFI Committee investigated and classified serious AEFI (SAE) according to Brighton Collaboration Criteria. RESULTS: Among 1053 enrolled children, 672 (64%) were reported to have a non-serious AEFI (NSAE) and 17 (2%) were reported to have a SAE. The most common AEFI were diarrhoea, fever, and rash, each reported by 355 (34%), 338 (33%), and 188 (18%) participants, respectively. Among 17 participants with SAE, eight were reported to have had seizures and five were hospitalised for seizures or other causes (respiratory symptoms, gastrointestinal illness, malaria). Four SAEs (deaths) occurred >28 days after vaccination. There were no reported cases of pre-specified or vaccine-related SAEs. We observed no significant difference in frequency or severity of adverse events among the study groups. CONCLUSIONS: Using comprehensive active surveillance monitoring, we did not identify any unexpected safety concerns among children aged <2 years receiving YF vaccination, including with the fractional doses. Although we identified a high number of both serious and non-serious AEFI, none were determined to be causally related to YF vaccination. These results provide evidence for the safety of fractional dose YF vaccination among children aged 9-23 months.
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Vacina contra Febre Amarela , Febre Amarela , Humanos , Lactente , Vacina contra Febre Amarela/efeitos adversos , Vacina contra Febre Amarela/administração & dosagem , Uganda/epidemiologia , Masculino , Feminino , Febre Amarela/prevenção & controle , Método Simples-Cego , Vacinação/efeitos adversos , Vacinação/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Esquemas de ImunizaçãoRESUMO
BACKGROUND: Severe malarial anaemia requiring blood transfusion is a life-threatening condition affecting millions of children in sub-Saharan Africa. Up to 40% of children with severe malarial anaemia have associated lactic acidosis. Lactic acidosis in these children is strongly associated with fatal outcomes and is corrected by blood transfusion. However, it is not known whether the storage age of blood for transfusion affects resolution of lactic acidosis. The objective of this pilot study was to evaluate the effect of blood storage age on resolution of lactic acidosis in children with severe malarial anaemia and demonstrate feasibility of conducting a large trial. METHODS: Children aged six to 59 months admitted to Acute Care Unit of Mulago Hospital (Kampala, Uganda) with severe malarial anaemia (haemoglobin ≤ 5 g/dL) and lactic acidosis (blood lactate ≥5 mmol/L), were randomly assigned to receive either blood of short storage age (one to 10 days) or long storage age (21-35 days) by gravity infusion. Seventy-four patients were enrolled and randomized to two equal-sized study arms. Physiological measurements, including blood lactate, oxygen saturation, haemoglobin, and vital signs, were taken at baseline, during and after transfusion. The primary outcome variable was the proportion of children whose lactic acidosis resolved by four hours after transfusion. RESULTS: Thirty-four of 37 (92%) of the children in the short storage treatment arm compared to 30/37 (81%) in the long storage arm achieved a blood lactate <5 mmol/L by four hours post transfusion (p value = 0.308). The mean time to lactic acidosis resolution was 2.65 hours (95% CI; 2.25-3.05) in the short storage arm, compared to 3.35 hours (95% CI; 2.60-4.10) in the long storage arm (p value = 0.264). CONCLUSION: Pilot data suggest that among children with severe malarial anaemia and lactic acidosis transfused with packed red blood cells, the storage age of blood does not affect resolution of lactic acidosis. The results support a larger and well-powered study which is under way. TRIAL REGISTRATION: clinicaltrials.gov NCT01580111.
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Acidose Láctica/terapia , Transfusão de Sangue/métodos , Malária/complicações , Pré-Escolar , Armazenamento de Medicamentos/métodos , Feminino , Hemoglobinas/análise , Humanos , Lactente , Ácido Láctico/sangue , Masculino , Oxigênio/sangue , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: A high prevalence of tuberculosis (TB) in children presenting with severe pneumonia has previously been reported in South Africa. However, little is known about TB among children with pneumonia in Uganda and other resource limited countries. Moreover, TB is associated with high morbidity and mortality among such children. We conducted this study to establish the burden of pulmonary TB in children admitted with severe pneumonia in our setting. METHODS: A cross-sectional study was conducted at Mulago, a National Referral and teaching hospital in Uganda. Hospitalised children 2 months to 12 years of age with severe pneumonia based on WHO case definition were enrolledfrom February to June 2011. Children with a previous TB diagnosis or receiving anti-TB treatment were excluded. Each child was screened for TB using Tuberculin skin test, Chest X-ray, induced sputum samples and blood culture for mycobacterium. Sputum smears were examined using fluorescent microscopy, and cultured on both Lowenstein Jensen media (LJ) and Mycobacterial Growth Indicator Tubes (MGIT). RESULTS: Of the 270 children with severe pneumonia who were recruited over a 5-month period in 2011, the incidence ratio of pulmonary TB in children admitted with severe pneumonia was 18.9% (95% CI 14.6 - 23.9). The proportion of culture confirmed PTB was 6.3% (95% CI 3.8 - 9.7). Age group under 1 year and 1 to 5 years (OR 2.8 (95% CI 1.7 - 7.4) and OR 2.4 (95% CI 1.05 - 5.9) respectively) were more likely to be associated with pulmonary TB compared to those children over 5 years of age. A history of TB smear positive contact was associated with pulmonary TB (OR 3.0 (95% CI 1.3-6.5). CONCLUSIONS: We found a high burden of pulmonary TB in children admitted with severe pneumonia. These data highlight the need for TB screening in children admitted with severe pneumonia so as to improve TB case finding and child survival.
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Efeitos Psicossociais da Doença , Pneumonia/complicações , Tuberculose Pulmonar/complicações , Criança , Pré-Escolar , Estudos Transversais , Hospitalização , Humanos , Incidência , Lactente , Modelos Logísticos , Análise Multivariada , Pneumonia/terapia , Índice de Gravidade de Doença , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , UgandaRESUMO
Introduction: Despite scale up of Option B+, long-term retention of women in HIV care during pregnancy and the postpartum period remains an important challenge. We compared adherence to clinic appointments and antiretroviral therapy (ART) at different follow-up time points between enrolment and 24 months postpartum among pregnant women living with HIV and initiating Option B+ randomized to a peer group support, community-based drug distribution and income-generating intervention called "Friends for Life Circles" (FLCs) versus the standard of care (SOC). Methods: Between 16 May 2016 and 12 September 2017, 540 ART-naïve pregnant women living with HIV at urban and rural health facilities in Uganda were enrolled in the study. Participants were randomized 1:1 to the FLC intervention or SOC and assessed for adherence to prevention of mother to child HIV transmission (PMTCT) clinic appointments at 6 weeks, 12 and 24 months postpartum, self-reported adherence to ART at 6 weeks, 6 and 24 months postpartum validated by plasma HIV-1 RNA viral load (VL) measured at the same time points, and HIV status and HIV-free survival of infants at 18 months postpartum. We used Log-rank and Chi-Square p-values to test the equality of Kaplan-Meier survival probabilities and hazard rates (HR) for failure to retain in care for any reason by study arm. Results: There was no significant difference in adherence to PMTCT clinic visits or to ART or in median viral loads between FLC and SOC arms at any follow-up time points. Retention in care through the end of study was high in both arms but significantly higher among participants randomized to FLC (86.7%) compared to SOC (79.3%), p=0.022. The adjusted HR of visit dropout was 2.5 times greater among participants randomized to SOC compared to FLC (aHR=2.498, 95% CI: 1.417 - 4.406, p=0.002). Median VL remained < 400 copies/ml in both arms at 6 weeks, 6 and 24 months postpartum. Conclusions: Our findings suggest that programmatic interventions that provide group support, community based ART distribution and income-generation activities may contribute to retention in PMTCT care, HIV-free survival of children born to women living with HIV, and to the elimination of mother to child HIV transmission (MTCT).
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BACKGROUND: We compared the results of a serum-based measles immunoglobulin M (IgM) test with results of tests using paired reconstituted dried filter paper blood spot (DBS) samples to assess the feasibility of using DBS samples for measles diagnostic procedures. METHODS: We collected 588 paired serum and DBS samples from 349 children aged 8 months through 12 years at Mulago Hospital in Kampala, Uganda; of these samples, 513 (87%) were collected from children with a clinical diagnosis of measles 0-33 days after rash, and 75(13%) were collected from children hospitalized for other reasons. Eluted DBS and serum samples were tested using a commercial measles IgM enzyme immunoassay. Detection of viral RNA was attempted on a subset of 20 DBS by reverse-transcriptase polymerase chain reaction. RESULTS: Among the 513 sample pairs collected from children with measles, the concordances for samples collected during days 0-6 and >1 week after rash were 95.7% and 100%, respectively (P<.01). The relative sensitivity and specificity of the DBS-based assay during the first week were 98.7% and 88.9%, respectively, and the sensitivity and specificity >1 week after rash were 100% and 100%, respectively. Viral RNA was detected in 5 (26%) of 19 DBS samples tested. Among 75 sample pairs collected from children hospitalized for other reasons, concordance was 94.7%. CONCLUSIONS: DBS samples are a feasible alternative sample for measles diagnostic procedures in high-incidence settings.
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Anticorpos Antivirais/sangue , Técnicas Imunoenzimáticas/métodos , Imunoglobulina M/sangue , Sarampo/sangue , Sarampo/diagnóstico , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Sarampo/epidemiologia , Papel , Manejo de Espécimes/métodos , Uganda/epidemiologiaRESUMO
Background: Pre-treatment HIV drug resistance is a threat to elimination of mother to child HIV transmission and could lead to virological failure among HIV-positive pregnant women. We analysed genotypic HIV drug resistance (HIVDR) of baseline samples of participants enrolled in the Option B+ clinical trial in Uganda. Methods: HIV-infected pregnant women attending antenatal care were enrolled from Uganda's National Referral Hospital (Mulago) and Mityana District general hospital and surrounding health centers (HCs). Genotypic HIV testing was performed on blood samples from the first 135 enrolled women out of a subset of 136 participants (25%) who had a baseline VL>1000 copies/mL as one sample failed to amplify. Results: 159/540 (29.4%) had a VL < 1000 copies/ml and 381/540 (70.6%) had a VL >1,000 copies/ml. Of the women with VL>1000 copies/ml, 32 (23.7%) had resistance mutations including 29/135 (21.5%) NNRTI mutations, 6/135 (4.4%) NRTI mutations and 3/135 (2.2%) had both NNRTI and NRTI mutations. The most common NNRTI resistance mutations were: K103KN (5), K103N (5), V179T (4) and E138A (4). Conclusions: One quarter of the HIV-infected pregnant women in this trial at baseline had NNRTI genotypic resistance mutations. Our findings support new WHO guidelines for first-line ART that were changed to dolutegravir-based regimens.
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Fármacos Anti-HIV , Farmacorresistência Viral , Infecções por HIV , HIV-1 , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez , Feminino , Humanos , Gravidez , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Infecções por HIV/transmissão , HIV-1/genética , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Mutação , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/genética , Complicações Infecciosas na Gravidez/prevenção & controle , Cuidado Pré-Natal , Uganda , Carga Viral/genéticaRESUMO
BACKGROUND: Transfusion-transmitted infections (TTIs) are a global health challenge. One new approach to reduce TTIs is the use of pathogen reduction technology (PRT). In vitro, Mirasol PRT reduces the infectious load in whole blood (WB) by at least 99%. However, there are limited in vivo data on the safety and efficacy of Mirasol PRT. The objective of the Mirasol Evaluation of Reduction in Infections Trial (MERIT) is to investigate whether Mirasol PRT of WB can prevent seven targeted TTIs (malaria, bacteria, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, hepatitis E virus, and human herpesvirus 8). METHODS: MERIT is a randomized, double-blinded, controlled clinical trial. Recruitment started in November 2019 and is expected to end in 2024. Consenting participants who require transfusion as medically indicated at three hospitals in Kampala, Uganda, will be randomized to receive either Mirasol-treated WB (n = 1000) or standard WB (n = 1000). TTI testing will be performed on donor units and recipients (pre-transfusion and day 2, day 7, week 4, and week 10 after transfusion). The primary endpoint is the cumulative incidence of one or more targeted TTIs from the Mirasol-treated WB vs. standard WB in a previously negative recipient for the specific TTI that is also detected in the donor unit. Log-binomial regression models will be used to estimate the relative risk reduction of a TTI by 10 weeks associated with Mirasol PRT. The clinical effectiveness of Mirasol WB compared to standard WB products in recipients will also be evaluated. DISCUSSION: Screening infrastructure for TTIs in low-resource settings has gaps, even for major TTIs. PRT presents a fast, potentially cost-effective, and easy-to-use technology to improve blood safety. MERIT is the largest clinical trial designed to evaluate the use of Mirasol PRT for WB. In addition, this trial will provide data on TTIs in Uganda. TRIAL REGISTRATION: Mirasol Evaluation of Reduction in Infections Trial (MERIT) NCT03737669 . Registered on 9 November 2018.
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Reação Transfusional , Plaquetas , Segurança do Sangue/métodos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , UgandaRESUMO
BACKGROUND: Despite effective antiretroviral therapy (ART), HIV-infected children on treatment have been observed to have cardiac abnormalities. We sought to determine the prevalence, types and factors associated with cardiac abnormalities among HIV-infected Ugandan children on combination ART. METHODS: We carried out a cross-sectional study from July 2012 to January 2013, at Joint Clinical Research Centre among HIV-infected children aged 1-18 years. Cardiac abnormalities were assessed using electrocardiography and echocardiography. CD4 counts, viral load and complete blood count were performed at enrollment. The prevalence of cardiac abnormalities was determined using simple proportions with the associated factors ascertained using logistic regression. RESULTS: Among 285 children recruited, the median (interquartile range) age was 9 (6-13) years, 54% were female; 72% were on first line combination ART. Their mean (±SD) CD4 count was 1092 (±868.7) cells/mm; median (interquartile range) viral load was 20 (20-76) copies/mL. Ninety-four percent had adherence to ART of more than 95%. Cardiac abnormalities were detected in 39 (13.7%) children. The most common abnormalities by electrocardiography and echocardiography were nonspecific T wave changes (4.6%) and pericardial disease (thickened pericardium with or without pericardial effusion; 2.8%), respectively. No factor assessed was found to be significantly associated occurrence of cardiac dysfunction. CONCLUSIONS: The prevalence of cardiac dysfunction among the HIV-infected children on ART was 13.7%, which was high, with nonspecific T wave changes and pericardial disease being the most frequent abnormalities observed. No factor assessed was found to be associated with cardiac dysfunction.
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Terapia Antirretroviral de Alta Atividade , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Cardiopatias/epidemiologia , Cardiopatias/etiologia , Adolescente , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Estudos Transversais , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Cardiopatias/diagnóstico , Cardiopatias/fisiopatologia , Humanos , Lactente , Masculino , Cooperação do Paciente , Prevalência , Fatores de Risco , Uganda/epidemiologia , Carga ViralRESUMO
Rheumatic heart disease (RHD) remains highly prevalent in resource-constrained settings around the world, including countries with high rates of HIV/AIDS. Although both are immune-mediated diseases, it is unknown whether HIV modifies the risk or progression of RHD. We performed screening echocardiography to determine the prevalence of latent RHD in 488 HIV-infected children aged 5-18 in Kampala, Uganda. The overall prevalence of borderline/definite RHD was 0.82% (95% confidence interval: 0.26% to 2.23%), which is lower than the published prevalence rates of 1.5%-4% among Ugandan children. There may be protective factors that decrease the risk of RHD in HIV-infected children.
Assuntos
Infecções por HIV/complicações , Cardiopatia Reumática/epidemiologia , Adolescente , Criança , Estudos Transversais , Progressão da Doença , Ecocardiografia , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Prevalência , Cardiopatia Reumática/complicações , Uganda/epidemiologiaRESUMO
BACKGROUND: Sickle cell anaemia is prevalent in sub Saharan Africa. While α+-thalassaemia is known to modulate sickle cell anaemia, its magnitude and significance in Uganda have hitherto not been described. OBJECTIVES: To determine the prevalence of α+thalassaemia among sickle cell anaemia patients in Mulago Hospital and to describe the clinical and laboratory findings in these patients. METHODS: A cross sectional study was carried out on patients with sickle cell anaemia in Kampala. Dried blood spots were used to analyze for the deletional α+ thalassaemia using multiplex polymerase chain reaction. RESULTS: Of the 142 patients with sickle cell anaemia, 110 (77.5%) had the αα+thalassaemia deletion. The gene frequency of (-α) was 0.425. Ninety one percent (100/110) of those with α+thalassaemia were heterozygous (αα/α-). Amongst the patients older than 60 months, 15 (83.3%) of those without αα+thalassaemia had significant hepatomegaly of greater than 4 cm compared to 36 (45.6%) of those with α+thalassaemia (p=0.003). CONCLUSION: The gene frequency of (-α) of 0.425 noted in this study is higher than that reported from many places in Africa. Concurrent alpha thalassemia might be a protective trait against significant hepatomegaly in sickle cell anaemia patients more than 60 months of age at Mulago hospital.
Assuntos
Anemia Falciforme/epidemiologia , Talassemia alfa/epidemiologia , Idoso , Anemia Falciforme/diagnóstico , Anemia Falciforme/genética , Estudos Transversais , Feminino , Frequência do Gene , Humanos , Masculino , Prevalência , Inquéritos e Questionários , Uganda/epidemiologia , Talassemia alfa/diagnóstico , Talassemia alfa/genéticaRESUMO
INTRODUCTION: Up to 30% of type-1 diabetes mellitus (T1DM) patients have co-existent thyroid autoimmunity with up to 50% of them having associated thyroid dysfunction. Routine screening for thyroid autoimmunity and dysfunction is recommended in all T1DM patients. However, this was not currently practiced in Ugandan paediatric diabetes clinics. There was also paucity of data regarding thyroid autoimmunity and dysfunction in African children and adolescents with diabetes mellitus. The objective of this study was to quantify the magnitude of thyroid autoimmunity and dysfunction in Ugandan children with TIDM. METHODS: This was a cross sectional descriptive study to determine the prevalence of thyroid autoantibodies and describe thyroid function among children and adolescents aged 1-19 years with diabetes mellitus attending the paediatric diabetes clinic at Mulago National Referral Hospital, Kampala, Uganda. Following enrollment, we obtained details of clinical history and performed physical examination. Blood (plasma) was assayed to determine levels of antibodies to thyroid peroxidase (antiTPO), free thyroxine (FT4) and thyrotropin (TSH). RESULTS: The prevalence of thyroid autoimmunity was 7.3% (5/69). All antiTPO positive subjects were post pubertal, aged between 13-17 years with females comprising 3/5 of the antiTPO positive subjects. All study subjects were clinically euthyroid; however, 7.3% (5/69) of the study subjects had subclinical hypothyroidism. CONCLUSION: These data strengthen the argument for routine screening of all diabetic children and adolescents for thyroid autoimmunity (particularly anti-TPO) as recommended by international guidelines. We also recommend evaluation of thyroid function in diabetic children and adolescents to minimize the risk of undiagnosed thyroid dysfunction.
Assuntos
Anticorpos/sangue , Doenças Autoimunes/imunologia , Diabetes Mellitus Tipo 1/complicações , Doenças da Glândula Tireoide/imunologia , Adolescente , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Iodeto Peroxidase/imunologia , Masculino , Programas de Rastreamento/métodos , Prevalência , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/epidemiologia , Tireotropina/imunologia , Tiroxina/imunologia , Uganda/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Data on paediatric reference laboratory values are limited for sub-Saharan Africa. OBJECTIVE: To describe the distribution of haematological and chemical pathology values among healthy infants from Malawi and Uganda. METHODS: A cross-sectional study was conducted among healthy infants, 0-6 months old, born to HIV-uninfected mothers recruited from two settings in Blantyre, Malawi and Kampala, Uganda. Chemical pathology and haematology parameters were determined using standard methods on blood samples. Descriptive analyses by age-group were performed based on 2004 Division of AIDS Toxicity Table age categories. Mean values and interquartile ranges were compared by site and age-group. RESULTS: A total of 541 infants were included altogether, 294 from Malawi and 247 from Uganda. Overall, the mean laboratory values were comparable between the two sites. Mean alkaline phosphatase levels were lower among infants aged ≤21 days while aspartate aminotransferase, creatinine, total bilirubin and gamma-glutamyl transferase were higher in those aged 0-7 days than in older infants. Mean haematocrit, haemoglobin and neutrophil counts were higher in the younger age-groups (<35 days) and overall were lower than US norms. Red and white blood cell counts tended to decrease after birth but increased after â¼2 months of age. Mean basophil counts were higher in Malawi than in Uganda in infants aged 0-1 and 2-7 days; mean counts for eosinophils (for age groups 8-21 or older) and platelets (for all age groups) were higher in Ugandan than in Malawian infants. Absolute lymphocyte counts increased with infant age. CONCLUSION: The chemical pathology and haematological values in healthy infants born to HIV-uninfected mothers were comparable in Malawi and Uganda and can serve as useful reference values in these settings.
Assuntos
Antropometria , Células Sanguíneas , Análise Química do Sangue , Fenômenos Fisiológicos Sanguíneos , Fatores Etários , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Malaui , Masculino , Gravidez , UgandaRESUMO
OBJECTIVES: To determine normal hematologic and selected blood chemistry values among healthy, full-term, non-HIV-exposed infants in Uganda and Malawi, and to determine the proportion of healthy babies with an apparent laboratory toxicity based on Division of AIDS toxicity tables. DESIGN: This was a cross-sectional laboratory study of infants from birth to 6 months of age. METHODS: Blood samples were collected from a total of 561 infants and analyzed according to age categories similar to those in the 2004 Division of AIDS toxicity tables. Select chemistry and hematology parameters were determined and values compared with those in the toxicity tables. RESULTS: In the first 56 days of life, there were few graded toxicities except for neutropenia in 2 of 10 (20%) Ugandan and 13 of 45 (29%) Malawian infants at birth. After 7 days, about 20% of the infants in Uganda and Malawi would have been classified as having a neutropenia whereas 47% and 53% of those more than 2 months of age in Uganda and Malawi respectively, would have been reported as having an abnormal hemoglobin. Chemistry findings were not different from US norms. CONCLUSIONS: These findings underscore the importance of establishing relevant local laboratory norms for infants.
Assuntos
Análise Química do Sangue , Infecções por HIV/epidemiologia , Infecções por HIV/patologia , Estudos Transversais , Feminino , Testes Hematológicos/métodos , Humanos , Lactente , Recém-Nascido , Malaui/epidemiologia , Masculino , Uganda/epidemiologia , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: To determine the utility of total lymphocyte count (TLC) in predicting the 12-month mortality in HIV-infected Ugandan children and to correlate TLC and CD4 cell %. DESIGN: This is a retrospective data analysis of clinical and laboratory data collected prospectively on 128 HIV-infected children in the HIV Network for Prevention Trials 012 trial. METHODS: TLC and CD4 cell % measurements were obtained at birth, 14 weeks, and 12, 24, 36, 48, and 60 months of age and assessed with respect to risk of death within 12 months. RESULTS: Median TLC per microliter (CD4 cell %) was 4150 (41%) at birth, 4900 (24%) at 12 months, 4300 (19%) at 24 months, 4150 (19%) at 36 months, 4100 (18%) at 48 months, and 3800 (20%) at 60 months. The highest risk of mortality within 12 months was 34% - 37% at birth and declined to 13%-15% at 24 months regardless of TLC measurement. The correlation between CD4 cell % and TLC was extremely low overall (r = 0.01). CONCLUSIONS: The TLC did not predict a risk of progression to death within 12 months in HIV-infected Ugandan children. Therefore, TLC alone may not be a useful surrogate marker for determining those children at highest risk of death, who require antiretroviral therapy most urgently.