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1.
Trop Med Int Health ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33151598

RESUMO

OBJECTIVE: Sickle cell disease is an important public health issue that is increasingly recognized as a substantial contributor to morbidity and early childhood mortality in sub-Saharan Africa. We aimed to provide information from large-scale, long-term sickle cell screening efforts in Africa. METHODS: We used nationally representative data from the centralized public health laboratory database in Uganda to examine epidemiological trends in sickle cell screening over a five-year period, comparing age and geographic adjustments to prevalence among different testing cohorts of children aged 0-24 months, and calculating screening coverage within high-burden districts. RESULTS: A total of 324,356 children aged 0-24 months were screened for sickle cell trait and disease from February 2014 to March 2019. A high national burden of sickle cell disease (0.9%) was confirmed among a cohort of samples co-tested with HIV. In the cohort of samples referred specifically for sickle cell testing, the overall prevalence of sickle cell disease was 9.7% and particularly elevated in high-burden districts where focused screening occurred. The majority of children were screened before age 4 months, but the sickle specific cohort had a larger proportion of affected children tested between age 5-9 months, coincident with onset of disease signs and symptoms. Successful screening coverage of sickle cell disease births was achieved in several high-burden districts. CONCLUSIONS: Examination and analysis of national sickle cell screening trends in Uganda documents the successes of focused screening strategies as an important step toward universal screening. With this evidence and increased healthcare provider knowledge, Uganda can optimize sickle cell diagnosis and management across the country.

2.
Int J Infect Dis ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33130198

RESUMO

OBJECTIVES: There is a high demand for SARS-CoV-2 testing to identify COVID-19 cases. Real-time, quantitative PCR (qRT-PCR) is the recommended diagnostic test but a number of constraints, including cost prevent its widespread implementation. The aim of this study was to evaluate a low cost, easy-to-use rapid antigen test for diagnosing COVID-19 at the point-of-care. METHODS: Nasopharyngeal swabs from suspect COVID-19 cases and from low-risk volunteers were tested on the STANDARD Q COVID-19 Ag Test and results compared with the qRT-PCR results. RESULTS: 262 samples were collected including 90 qRT-PCR positives. The majority were from males (89%) with a mean age of 34 years and only 13 (14%) of the positives were mildly symptomatic. Sensitivity and specificity of the antigen test were 70.0% (95% CI: 60 - 79) and 92% (95% CI: 87 - 96) respectively; diagnostic accuracy was 84% (95% CI: 79 - 88). The antigen test was more likely to be positive in samples with qRT-PCR Ct values ≤29 reaching a sensitivity of 92%. CONCLUSIONS: The STANDARD Q COVID-19 Ag Test performed less than optimally in this evaluation. However, the test may still have an important role to play early in infection when timely access to molecular testing is not available but results should be confirmed by qRT-PCR.

3.
J Antimicrob Chemother ; 75(5): 1280-1289, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32025714

RESUMO

OBJECTIVES: We implemented the WHO cross-sectional survey protocol to determine rates of HIV viral load (VL) suppression (VLS), and weighted prevalence, predictors and patterns of acquired drug resistance (ADR) in individuals with virological failure (VF) defined as VL ≥1000 copies/mL. METHODS: We enrolled 547 and 1064 adult participants on first-line ART for 12 (±3) months (ADR12) and ≥48 months (ADR48), respectively. Dried blood spots and plasma specimens were collected for VL testing and genotyping among the VFs. RESULTS: VLS was 95.0% (95% CI 93.4%-96.5%) in the ADR12 group and 87.9% (95% CI 85.0%-90.9%) in the ADR48 group. The weighted prevalence of ADR was 96.1% (95% CI 72.9%-99.6%) in the ADR12 and 90.4% (95% CI 73.6-96.8%) in the ADR48 group, out of the 30 and 95 successful genotypes in the respective groups. Initiation on a zidovudine-based regimen compared with a tenofovir-based regimen was significantly associated with VF in the ADR48 group; adjusted OR (AOR) 1.96 (95% CI 1.13-3.39). Independent predictors of ADR in the ADR48 group were initiation on a zidovudine-based regimen compared with tenofovir-based regimens, AOR 3.16 (95% CI 1.34-7.46) and ART duration of ≥82 months compared with <82 months, AOR 1.92 (95% CI 1.03-3.59). CONCLUSIONS: While good VLS was observed, the high prevalence of ADR among the VFs before they underwent the recommended three intensive adherence counselling (IAC) sessions followed by repeat VL testing implies that IAC prior to treatment switching may be of limited benefit in improving VLS.

4.
Clin Infect Dis ; 71(7): 1726-1731, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31679007

RESUMO

BACKGROUND: Detectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization recommends CrAg screening for human immunodeficiency virus-positive persons with CD4 count <100 cells/µL initiating antiretroviral therapy (ART). However, an increasing proportion of patients with cryptococcosis are now ART experienced. Whether CrAg screening is cost-effective in those with virologic failure is unknown. METHODS: We retrospectively performed nationwide plasma CrAg testing among ART-experienced Ugandan adults with virologic failure (≥1000 copies/mL) using leftover plasma after viral load testing during September 2017-January 2018. For those who were CrAg positive, we obtained ART history, meningitis occurrence, and 6-month survival via medical records review. RESULTS: Among 1186 subjects with virologic failure, 35 (3.0%) were CrAg positive with median ART duration of 41 months (interquartile range, 10-84 months). Among 25 subjects with 6-month outcomes, 16 (64%) survived, 7 (28%) died, and 2 (8%) were lost. One survivor had suffered cryptococcal meningitis 2 years prior. Two others developed cryptococcal meningitis and survived. Five survivors were known to have received fluconazole. Thus, meningitis-free survival at 6 months was 61% (14/23). Overall, 91% (32/35) of CrAg-positive persons had viral load ≥5000 copies/mL compared with 64% (735/1151) of CrAg-negative persons (odds ratio, 6.0 [95% confidence interval, 1.8-19.8]; P = .001). CrAg prevalence was 4.2% (32/768) among those with viral loads ≥5000 copies/mL and 0.7% (3/419) among those with viral loads <5000 copies/mL. CONCLUSIONS: In addition to the CD4 threshold of <100 cells/µL, reflexive CrAg screening should be considered in persons failing ART in Uganda with viral loads ≥5000 copies/mL.

5.
Front Immunol ; 11: 576663, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33584643

RESUMO

Understanding how immunity to malaria is affected by declining transmission is important to aid vaccine design and understand disease resurgence. Both IgG subclasses and avidity of antigen-specific responses are important components of an effective immune response. Using a multiplex bead array assay, we measured the total IgG, IgG subclasses, and avidity profiles of responses to 18 P. falciparum blood stage antigens in samples from 160 Ugandans collected at two time points during high malaria transmission and two time points following a dramatic reduction in transmission. Results demonstrated that, for the antigens tested, (i) the rate of decay of total IgG following infection declined with age and was driven consistently by the decrease in IgG3 and occasionally the decrease in IgG1; (ii) the proportion of IgG3 relative to IgG1 in the absence of infection increased with age; (iii) the increase in avidity index (the strength of association between the antibody and antigen) following infection was largely due to a rapid loss of non-avid compared to avid total IgG; and (iv) both avid and non-avid total IgG in the absence of infection increased with age. Further studies are required to understand the functional differences between IgG1 and IgG3 in order to determine their contribution to the longevity of protective immunity to malaria. Measuring changes in antibody avidity may be a better approach of detecting affinity maturation compared to avidity index due to the differential expansion and contraction of high and low avidity total IgG.

6.
BMC Infect Dis ; 19(1): 516, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185939

RESUMO

BACKGROUND: A cholera outbreak started on 29 February in Bwikhonge Sub-county, Bulambuli District in Eastern Uganda. Local public health authorities implemented initial control measures. However, in late March, cases sharply increased in Bwikhonge Sub-county. We investigated the outbreak to determine its scope and mode of transmission, and to inform control measures. METHODS: We defined a suspected case as sudden onset of watery diarrhea from 1 March 2016 onwards in a resident of Bulambuli District. A confirmed case was a suspected case with positive stool culture for V. cholerae. We conducted descriptive epidemiologic analysis of the cases to inform the hypothesis on mode of transmission. To test the hypothesis, we conducted a case-control study involving 100 suspected case-patients and 100 asymptomatic controls, individually-matched by residence village and age. We collected seven water samples for laboratory testing. RESULTS: We identified 108 suspected cases (attack rate: 1.3%, 108/8404), including 7 confirmed cases. The case-control study revealed that 78% (78/100) of case-patients compared with 51% (51/100) of control-persons usually collected drinking water from the nearby Cheptui River (ORMH = 7.8, 95% CI = 2.7-22); conversely, 35% (35/100) of case-patients compared with 54% (54/100) of control-persons usually collected drinking water from borehole pumps (ORMH = 0.31, 95% CI = 0.13-0.65). The index case in Bwikhonge Sub-county had onset on 29 February but the outbreak had been on-going in the neighbouring sub-counties in the previous 3 months. V. cholera was isolated in 2 of the 7 river water samples collected from different locations. CONCLUSIONS: We concluded that this cholera outbreak was caused by drinking contaminated water from Cheptui River. We recommended boiling and/or treating drinking water, improved sanitation, distribution of chlorine tablets to the affected villages, and as a long-term solution, construction of more borehole pumps. After implementing preventive measures, the number of cases declined and completely stopped after 6th April.


Assuntos
Cólera/epidemiologia , Cólera/etiologia , Surtos de Doenças , Água Potável/microbiologia , Rios/microbiologia , Poluição da Água , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Diarreia/epidemiologia , Diarreia/microbiologia , Surtos de Doenças/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saneamento , Uganda/epidemiologia , Vibrio cholerae/isolamento & purificação , Poluição da Água/efeitos adversos , Adulto Jovem
7.
Pediatr Blood Cancer ; 66(8): e27807, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31094093

RESUMO

BACKGROUND: The Uganda Sickle Surveillance Study provided evidence for a large sickle burden among HIV-exposed infants in Uganda. To date, however, no large scale screening program has been developed for Central or East Africa. METHODS: A 3-year targeted sickle cell screening project in Uganda was designed by the Ministry of Health to (1) determine sickle cell trait and disease prevalence within high-burden districts, (2) document the prevalence among HIV-exposed and nonexposed children, (3) confirm previously suggested HIV comorbidity, and (4) estimate the co-inheritance of known genetic modifiers of sickle cell disease. RESULTS: A total of 163 334 dried blood spot samples collected between April 2015 and March 2018 were analyzed, including 112 352 samples within the HIV Early Infant Diagnosis program. A high burden with >1% sickle cell disease was found within targeted East Central and Mid-Northern districts, in both HIV-exposed and nonexposed children. Based on crude birth-rate data, 236 905 sickle cell trait births and 16 695 sickle cell disease births will occur annually in Uganda. Compared to sickle cell disease without HIV, the odds ratio of having sickle cell disease plus HIV was 0.50 (95% confidence interval = 0.40-0.64, P < .0001). Alpha-thalassemia trait and G6PD deficiency were common with sickle cell disease, but with different geospatial distribution. CONCLUSIONS: High sickle cell burden and potential HIV comorbidity are confirmed in Uganda. Genetic modifiers are common and likely influence laboratory and clinical phenotypes. These prospective data document that targeted sickle cell screening is feasible and effective in Uganda, and support development of district-level comprehensive care programs.


Assuntos
Anemia Falciforme/diagnóstico , Genes Modificadores , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Infecções por HIV/diagnóstico , Programas de Rastreamento/métodos , Talassemia alfa/diagnóstico , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Anemia Falciforme/genética , Pré-Escolar , Comorbidade , Feminino , Seguimentos , Deficiência de Glucosefosfato Desidrogenase/complicações , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/genética , HIV/genética , HIV/isolamento & purificação , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/genética , Humanos , Lactente , Recém-Nascido , Masculino , Prevalência , Prognóstico , Estudos Prospectivos , Talassemia alfa/complicações , Talassemia alfa/epidemiologia , Talassemia alfa/genética
8.
Wellcome Open Res ; 4: 171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32954012

RESUMO

Background: In the last decade, Low- and Middle-Income Countries (LMICs) have set up Biobanks to collect human biological materials and associated data for genomic research and public health purposes. Biobanking gives rise to ethical challenges, such as informed consent, benefit sharing, confidentiality, ownership, commercialization and public participation which are harder to navigate in LMIC settings due to disparities in research infrastructure and capacity.  This paper summarizes presentations on Biobank related case studies from two countries, with a focus on challenges in the regulatory and governance framework and suggestions on how to mitigate them.   Methods: Two case studies of Biobanks from LMICs have been used . The case studies were presented at the 2018 Global Forum on Bioethics in Research (GFBR) meeting on the "Ethics of data sharing and Biobanking in health research". Results: The case studies show that an integrated, well-regulated platform for human biological materials and data ensures good quality of human biological materials, saves resources and promotes mutual collaboration of work among researchers. National regulatory bodies are required to generate Biobanking guidelines and policies to facilitate guidance to the rapidly changing landscape of science. Discussion: In general, LMICs have weaker research regulatory infrastructure and governance mechanisms for Biobanks than high-income countries. This has increased the fear of exploitation i.e. unfair distribution of risks and benefits. Establishment of Biobanks and producing effective scientific outcomes based on the Biobanking resources is difficult without a proper legislative, regulatory and governance framework. Conclusion: These two case studies from different LMICs settings show that although in both settings there is strong awareness of the scientific and population health value of Biobanks and strong commitment to their establishment, regulatory and ethical guidance show gaps that need to be addressed.

9.
Wellcome Open Res ; 4: 26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32518839

RESUMO

Background: Antibody responses have been used to characterise transmission and exposure history in malaria-endemic settings for over a decade. Such studies have typically been conducted on well-standardised enzyme-linked immunosorbent assays (ELISAs). However, recently developed quantitative suspension array technologies (qSAT) are now capable of high-throughput and multiplexed screening of up to hundreds of analytes at a time. This study presents a customised protocol for the Luminex MAGPIX © qSAT using a diverse set of malaria antigens. The aim is to develop a standardised assay for routine serological surveillance that is implementable across laboratories and epidemiological settings. Methods: A panel of eight Plasmodium falciparum recombinant antigens, associated with long- and short-lived antibody responses, was designed for the Luminex MAGPIX © platform. The assay was optimised for key steps in the protocol: antigen-bead coupling concentration, buffer composition, serum sample dilution, and bead storage conditions. Quality control procedures and data normalisation methods were developed to address high-throughput assay processing.  Antigen-specific limits of quantification (LOQs) were also estimated using both in-house and WHO reference serum as positive controls. Results: Antigen-specific bead coupling was optimised across five serum dilutions and two positive controls, resulting in concentrations operational within stable analytical ranges. Coupled beads were stable after storage at room temperature (22°C) for up to eight weeks. High sensitivity and specificity for distinguishing positive and negative controls at serum sample dilutions of 1:500 (AUC 0.94 95%CI 0.91-0.96) and 1:1000 (AUC 0.96 95%CI 0.94-0.98) were observed. LOQs were also successfully estimated for all analytes but varied by antigen and positive control. Conclusions: This study demonstrates that developing a standardised malaria-specific qSAT protocol for a diverse set of antigens is achievable, though further optimisations may be required. Quality control and data standardisation methods may also be useful for future analysis of large sero-epidemiological surveys.

11.
Elife ; 72018 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-30044224

RESUMO

Fundamental gaps remain in our understanding of how immunity to malaria develops. We used detailed clinical and entomological data from parallel cohort studies conducted across the malaria transmission spectrum in Uganda to quantify the development of immunity against symptomatic P. falciparum as a function of age and transmission intensity. We focus on: anti-parasite immunity (i.e. ability to control parasite densities) and anti-disease immunity (i.e. ability to tolerate higher parasite densities without fever). Our findings suggest a strong effect of age on both types of immunity, not explained by cumulative-exposure. They also show an independent effect of exposure, where children living in moderate/high transmission settings develop immunity faster as transmission increases. Surprisingly, children in the lowest transmission setting appear to develop immunity more efficiently than those living in moderate transmission settings. Anti-parasite and anti-disease immunity develop in parallel, reducing the probability of experiencing symptomatic malaria upon each subsequent P. falciparum infection.


Assuntos
Imunidade , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Parasitos/imunologia , Fatores Etários , Animais , Pré-Escolar , Feminino , Humanos , Incidência , Modelos Lineares , Malária Falciparum/epidemiologia , Masculino , Mutação/genética , Prevalência , Probabilidade , Temperatura , Uganda/epidemiologia
12.
PLoS Med ; 15(7): e1002606, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30016328

RESUMO

BACKGROUND: Intermittent preventive treatment of malaria in pregnancy (IPTp) with dihydroartemisinin-piperaquine (IPTp-DP) has been shown to reduce the burden of malaria during pregnancy compared to sulfadoxine-pyrimethamine (IPTp-SP). However, limited data exist on how IPTp regimens impact malaria risk during infancy. We conducted a double-blinded randomized controlled trial (RCT) to test the hypothesis that children born to mothers given IPTp-DP would have a lower incidence of malaria during infancy compared to children born to mothers who received IPTp-SP. METHODS AND FINDINGS: We compared malaria metrics among children in Tororo, Uganda, born to women randomized to IPTp-SP given every 8 weeks (SP8w, n = 100), IPTp-DP every 8 weeks (DP8w, n = 44), or IPTp-DP every 4 weeks (DP4w, n = 47). After birth, children were given chemoprevention with DP every 12 weeks from 8 weeks to 2 years of age. The primary outcome was incidence of malaria during the first 2 years of life. Secondary outcomes included time to malaria from birth and time to parasitemia following each dose of DP given during infancy. Results are reported after adjustment for clustering (twin gestation) and potential confounders (maternal age, gravidity, and maternal parasitemia status at enrolment).The study took place between June 2014 and May 2017. Compared to children whose mothers were randomized to IPTp-SP8w (0.24 episodes per person year [PPY]), the incidence of malaria was higher in children born to mothers who received IPTp-DP4w (0.42 episodes PPY, adjusted incidence rate ratio [aIRR] 1.92; 95% CI 1.00-3.65, p = 0.049) and nonsignificantly higher in children born to mothers who received IPT-DP8w (0.30 episodes PPY, aIRR 1.44; 95% CI 0.68-3.05, p = 0.34). However, these associations were modified by infant sex. Female children whose mothers were randomized to IPTp-DP4w had an apparently 4-fold higher incidence of malaria compared to female children whose mothers were randomized to IPTp-SP8w (0.65 versus 0.20 episodes PPY, aIRR 4.39, 95% CI 1.87-10.3, p = 0.001), but no significant association was observed in male children (0.20 versus 0.28 episodes PPY, aIRR 0.66, 95% CI 0.25-1.75, p = 0.42). Nonsignificant increases in malaria incidence were observed among female, but not male, children born to mothers who received DP8w versus SP8w. In exploratory analyses, levels of malaria-specific antibodies in cord blood were similar between IPTp groups and sex. However, female children whose mothers were randomized to IPTp-DP4w had lower mean piperaquine (PQ) levels during infancy compared to female children whose mothers received IPTp-SP8w (coef 0.81, 95% CI 0.65-1.00, p = 0.048) and male children whose mothers received IPTp-DP4w (coef 0.72, 95% CI 0.57-0.91, p = 0.006). There were no significant sex-specific differences in PQ levels among children whose mothers were randomized to IPTp-SP8w or IPTp-DP8w. The main limitations were small sample size and childhood provision of DP every 12 weeks in infancy. CONCLUSIONS: Contrary to our hypothesis, preventing malaria in pregnancy with IPTp-DP in the context of chemoprevention with DP during infancy does not lead to a reduced incidence of malaria in childhood; in this setting, it may be associated with an increased incidence of malaria in females. Future studies are needed to better understand the biological mechanisms of in utero drug exposure on drug metabolism and how this may affect the dosing of antimalarial drugs for treatment and prevention during infancy. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02163447.


Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Malária Falciparum/prevenção & controle , Complicações Parasitárias na Gravidez/prevenção & controle , Pirimetamina/administração & dosagem , Quinolinas/administração & dosagem , Sulfadoxina/administração & dosagem , Adolescente , Adulto , Antimaláricos/efeitos adversos , Artemisininas/efeitos adversos , Pré-Escolar , Método Duplo-Cego , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Malária Falciparum/transmissão , Gravidez , Complicações Parasitárias na Gravidez/epidemiologia , Complicações Parasitárias na Gravidez/parasitologia , Pirimetamina/efeitos adversos , Quinolinas/efeitos adversos , Sulfadoxina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Uganda/epidemiologia , Adulto Jovem
13.
Sci Rep ; 8(1): 8896, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29891920

RESUMO

Abscisic acid (ABA) is an ancient stress hormone and is detectable in a wide variety of organisms where it regulates innate immunity and inflammation. Previously, we showed that oral supplementation with ABA decreased parasitemia in a mouse model of malaria, decreased liver and spleen pathology and reduced parasite transmission to mosquitoes. Here, we report that higher circulating ABA levels were associated with a reduced risk of symptomatic malaria in a cohort of Plasmodium falciparum-infected Ugandan children. To understand possible mechanisms of ABA protection in malaria, we returned to our mouse model to show that ABA effects on Plasmodium yoelii 17XNL infection were accompanied by minimal effects on complete blood count and blood chemistry analytes, suggesting a benefit to host health. In addition, orally delivered ABA induced patterns of gene expression in mouse liver and spleen that suggested enhancement of host anti-parasite defenses. To test these inferences, we utilized passive immunization and knockout mice to demonstrate that ABA supplementation increases circulating levels of protective, parasite-specific IgG and requires caspase-1 to reduce parasitemia. Collectively, ABA induces host responses that ameliorate infection and disease in an animal model and suggest that further studies of ABA in the context of human malaria are warranted.


Assuntos
Ácido Abscísico/sangue , Caspase 1/metabolismo , Imunoglobulina G/imunologia , Malária/imunologia , Ácidos , Animais , Doenças Assintomáticas , Criança , Pré-Escolar , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Knockout , Reguladores de Crescimento de Planta , Plasmodium falciparum/imunologia , Plasmodium yoelii/imunologia , Uganda
14.
J Int AIDS Soc ; 21(2)2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29479861

RESUMO

INTRODUCTION: Despite notable progress towards PMTCT, only 50% of HIV-exposed infants in sub-Saharan Africa were tested within the first 2 months of life and only 30% of HIV-infected infants are on antiretroviral treatment. This study assessed HIV prevalence in infants and children receiving care at various service entry points in primary healthcare facilities in Uganda. METHODS: A total of 3600 infants up to 24 months of age were systematically enrolled and tested at four regional hospitals across Uganda. Six hundred infants were included and tested from six facility entry points: PMTCT, immunization, inpatient, nutrition, outpatient and community outreach services. FINDINGS: The traditional EID entry point, PMTCT, had a prevalence of 3.8%, representing 19.6% of the total HIV-positive infants identified in the study. Fifty percent of the 117 identified HIV-positive infants were found in the nutrition wards, which had a prevalence of 9.8% (p < 0.001 compared to PMTCT). Inpatient wards had a prevalence of 3.5% and yielded 17.9% of the HIV-positive infants identified. Infants tested at immunization wards and through outreach services identified 0.8% and 1.7% of the HIV-positive infants respectively, and had a prevalence of less than 0.3%. CONCLUSIONS: Expanding routine early infant diagnosis screening beyond the traditional PMTCT setting to nutrition and inpatient entry points will increase the identification of HIV-infected infants. Careful reflection for appropriate testing strategies, such as maternal re-testing to identify new HIV infections and HIV-exposed infants in need of follow-up testing and care, at immunization and outreach services should be considered given the expectedly low prevalence rates. These findings may help HIV care programmes significantly expand testing to improve access to early infant diagnosis and paediatric treatment.


Assuntos
Infecções por HIV/epidemiologia , Instituições de Assistência Ambulatorial , Estudos Transversais , Feminino , Infecções por HIV/terapia , Humanos , Lactente , Pacientes Internados , Masculino , Prevalência , Estudos Prospectivos , Uganda/epidemiologia
15.
J Acquir Immune Defic Syndr ; 77(3): 331-336, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29206722

RESUMO

BACKGROUND: Data on the performance and utility of rapid serological tests in infants to determine HIV exposure are unclear and in some instances contradictory. This study sought to understand the performance of rapid serological tests in high HIV burden, high Option B+ coverage settings to be used as an HIV exposure screening tool. METHODS: A total of 3600 infants up to 24 months of age at 4 regional hospitals in Uganda were systematically enrolled and tested simultaneously using both HIV rapid serological and nucleic acid-based tests. RESULTS: Only 58 of the 94 HIV-positive infants who received both rapid serological and nucleic acid-based tests were positive with the rapid serological test (sensitivity: 61.7%; 95% confidence interval: 51.1 to 71.5). Using rapid serological tests to screen infants for exposure to HIV and follow-up nucleic acid-based testing would have missed 38.3% (36 of 94) of HIV-positive infants. Finally, several HIV-positive infants who were negative by rapid serological test presented to well-child entry points and were considered healthy. All 3 HIV-positive infants presenting to outreach and immunization were negative by rapid serological testing and 73% (8 of 11) presenting to outpatient. CONCLUSIONS: These data suggest that the use of rapid serological tests may have inadequate performance as an indicator of exposure and potential HIV infection among infants presenting at both well-child (immunization and community outreach) and sick-infant (nutrition and inpatient) entry points. To improve the identification of HIV-positive infants, nucleic acid-based testing should instead be considered in infants aged younger than 18 months.


Assuntos
Exposição Ambiental , Infecções por HIV/diagnóstico , Testes Sorológicos/métodos , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Programas de Rastreamento/métodos , Técnicas de Diagnóstico Molecular/métodos , Estudos Prospectivos , Sensibilidade e Especificidade , Uganda
16.
BMC Infect Dis ; 17(1): 326, 2017 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-28468608

RESUMO

BACKGROUND: Despite the growing number of people on antiretroviral therapy (ART), there is limited information about virological non-suppression and its determinants among HIV-positive (HIV+) individuals enrolled in HIV care in many resource-limited settings. We estimated the proportion of virologically non-suppressed patients, and identified the factors associated with virological non-suppression. METHODS: We conducted a descriptive cross-sectional study using routinely collected program data from viral load (VL) samples collected across the country for testing at the Central Public Health Laboratories (CPHL) in Uganda. Data were generated between August 2014 and July 2015. We extracted data on socio-demographic, clinical and VL testing results. We defined virological non-suppression as having ≥1000 copies of viral RNA/ml of blood for plasma or ≥5000 copies of viral RNA/ml of blood for dry blood spots. We used logistic regression to identify factors associated with virological non-suppression. RESULTS: The study was composed of 100,678 patients; of these, 94,766(94%) were for routine monitoring, 3492(4%) were suspected treatment failures while 1436(1%) were repeat testers after suspected failure. The overall proportion of non-suppression was 11%. Patients on routine monitoring registered the lowest (10%) proportion of non-suppressed patients. Virological non-suppression was higher among suspected treatment failures (29%) and repeat testers after suspected failure (50%). Repeat testers after suspected failure were six times more likely to have virological non-suppression (ORadj = 6.3, 95%CI = 5.5-7.2) when compared with suspected treatment failures (ORadj = 3.3, 95%CI = 3.0-3.6). The odds of virological non-suppression decreased with increasing age, with children aged 0-4 years (ORadj = 5.3, 95%CI = 4.6-6.1) and young adolescents (ORadj = 4.1, 95%CI = 3.7-4.6) registering the highest odds. Poor adherence (ORadj = 3.4, 95%CI = 2.9-3.9) and having active TB (ORadj = 1.9, 95%CI = 1.6-2.4) increased the odds of virological non-suppression. However, being on second/third line regimens (ORadj = 0.86, 95%CI = 0.78-0.95) protected patients against virological non-suppression. CONCLUSION: Young age, poor adherence and having active TB increased the odds of virological non-suppression while second/third line ART regimens were protective against non-suppression. We recommend close follow up and intensified targeted adherence support for repeat testers after suspected failure, children and adolescents.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Cooperação do Paciente , RNA Viral/sangue , Falha de Tratamento , Uganda , Carga Viral , Adulto Jovem
17.
Malar J ; 16(1): 67, 2017 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-28183299

RESUMO

BACKGROUND: People living in malaria endemic areas acquire protection from severe malaria quickly, but protection from clinical disease and control of parasitaemia is acquired only after many years of repeated infections. Antibodies play a central role in protection from clinical disease; however, protective antibodies are slow to develop. This study sought to investigate the influence of Plasmodium falciparum exposure on the acquisition of high-avidity antibodies to P. falciparum antigens, which may be associated with protection. METHODS: Cross-sectional surveys were performed in children and adults at three sites in Uganda with varied P. falciparum transmission intensity (entomological inoculation rates; 3.8, 26.6, and 125 infectious bites per person per year). Sandwich ELISA was used to measure antibody responses to two P. falciparum merozoite surface antigens: merozoite surface protein 1-19 (MSP1-19) and apical membrane antigen 1 (AMA1). In individuals with detectable antibody levels, guanidine hydrochloride (GuHCl) was added to measure the relative avidity of antibody responses by ELISA. RESULTS: Within a site, there were no significant differences in median antibody levels between the three age groups. Between sites, median antibody levels were generally higher in the higher transmission sites, with differences more apparent for AMA-1 and in ≥5 year group. Similarly, median avidity index (proportion of high avidity antibodies) showed no significant increase with increasing age but was significantly lower at sites of higher transmission amongst participants ≥5 years of age. Using 5 M GuHCl, the median avidity indices in the ≥5 year group at the highest and lowest transmission sites were 19.9 and 26.8, respectively (p = 0.0002) for MSP1-19 and 12.2 and 17.2 (p = 0.0007) for AMA1. CONCLUSION: Avidity to two different P. falciparum antigens was lower in areas of high transmission intensity compared to areas with lower transmission. Appreciation of the mechanisms behind these findings as well as their clinical consequences will require additional investigation, ideally utilizing longitudinal data and investigation of a broader array of responses.


Assuntos
Anticorpos Antiprotozoários/sangue , Afinidade de Anticorpos , Malária Falciparum/imunologia , Malária Falciparum/transmissão , Plasmodium falciparum/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Malária Falciparum/epidemiologia , Masculino , Merozoítos/imunologia , Pessoa de Meia-Idade , Uganda/epidemiologia , Adulto Jovem
18.
Am J Trop Med Hyg ; 96(2): 330-334, 2017 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-27895271

RESUMO

Understanding variations in malaria transmission and exposure is critical to identify populations at risk and enable better targeting of interventions. The indigenous Batwa of southwestern Uganda have a disproportionate burden of malaria infection compared with their non-indigenous neighbors. To better understand the individual- and community-level determinants of malaria exposure, a seroepidemiological study was conducted in 10 local council cells in Kanungu District, Uganda, in April 2014. The Batwa had twice the odds of being seropositive to two Plasmodium falciparum-specific antigens, apical membrane antigen-1 and merozoite surface protein-119, compared with the non-indigenous Bakiga (odds ratio = 2.08, 95% confidence interval = 1.51-2.88). This trend was found irrespective of altitude level and after controlling for cell location. Seroconversion rates in the Batwa were more than twice those observed in the Bakiga. For the Batwa, multiple factors may be associated with higher exposure to malaria and antibody levels relative to their non-indigenous neighbors.


Assuntos
Formação de Anticorpos/imunologia , Malária Falciparum/imunologia , Adolescente , Adulto , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Malária Falciparum/epidemiologia , Masculino , Proteínas de Membrana/imunologia , Proteína 1 de Superfície de Merozoito/imunologia , Grupos Populacionais/estatística & dados numéricos , Proteínas de Protozoários/imunologia , Fatores de Risco , Estudos Soroepidemiológicos , Uganda/epidemiologia , Adulto Jovem
19.
MMWR Morb Mortal Wkly Rep ; 65(46): 1285-1290, 2016 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-27880749

RESUMO

Pediatric human immunodeficiency virus (HIV) infection remains an important public health issue in resource-limited settings. In 2015, 1.4 million children aged <15 years were estimated to be living with HIV (including 170,000 infants born in 2015), with the vast majority living in sub-Saharan Africa (1). In 2014, 150,000 children died from HIV-related causes worldwide (2). Access to timely HIV diagnosis and treatment for HIV-infected infants reduces HIV-associated mortality, which is approximately 50% by age 2 years without treatment (3). Since 2011, the annual number of HIV-infected children has declined by 50%. Despite this gain, in 2014, only 42% of HIV-exposed infants received a diagnostic test for HIV (2), and in 2015, only 51% of children living with HIV received antiretroviral therapy (1). Access to services for early infant diagnosis of HIV (which includes access to testing for HIV-exposed infants and clinical diagnosis of HIV-infected infants) is critical for reducing HIV-associated mortality in children aged <15 years. Using data collected from seven countries supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), progress in the provision of HIV testing services for early infant diagnosis was assessed. During 2011-2015, the total number of HIV diagnostic tests performed among HIV-exposed infants within 6 weeks after birth (tests for early infant diagnosis of HIV), as recommended by the World Health Organization (WHO) increased in all seven countries (Cote d'Ivoire, the Democratic Republic of the Congo, Haiti, Malawi, South Africa, Uganda, and Zambia); however, in 2015, the rate of testing for early infant diagnosis among HIV-exposed infants was <50% in five countries. HIV positivity among those tested declined in all seven countries, with three countries (Cote d'Ivoire, the Democratic Republic of the Congo, and Uganda) reporting >50% decline. The most common challenges for access to testing for early infant diagnosis included difficulties in specimen transport, long turnaround time between specimen collection and receipt of results, and limitations in supply chain management. Further reductions in HIV mortality in children can be achieved through continued expansion and improvement of services for early infant diagnosis in PEPFAR-supported countries, including initiatives targeted to reach HIV-exposed infants, ensure access to programs for early infant diagnosis of HIV, and facilitate prompt linkage to treatment for children diagnosed with HIV infection.


Assuntos
Diagnóstico Precoce , Infecções por HIV/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , África ao Sul do Saara , Região do Caribe , Feminino , Infecções por HIV/transmissão , Humanos , Lactente , Transmissão Vertical de Doença Infecciosa , Gravidez
20.
J Infect Dis ; 214(7): 1072-80, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27481862

RESUMO

BACKGROUND: Plasmodium falciparum malaria remains a leading cause of childhood morbidity and mortality. There are important gaps in our understanding of the factors driving the development of antimalaria immunity as a function of age and exposure. METHODS: We used data from a cohort of 93 children participating in a clinical trial in Tororo, Uganda, an area of very high exposure to P. falciparum We jointly quantified individual heterogeneity in the risk of infection and the development of immunity against infection and clinical disease. RESULTS: Results showed significant heterogeneity in the hazard of infection and independent effects of age and cumulative number of infections on the risk of infection and disease. The risk of developing clinical malaria upon infection decreased on average by 6% (95% confidence interval [CI], 0%-12%) for each additional year of age and by 2% (95% CI, 1%-3%) for each additional prior infection. Children randomly assigned to receive dihydroartemisinin-piperaquine for treatment appeared to develop immunity more slowly than those receiving artemether-lumefantrine. CONCLUSIONS: Heterogeneity in P. falciparum exposure and immunity can be independently evaluated using detailed longitudinal studies. Improved understanding of the factors driving immunity will provide key information to anticipate the impact of malaria-control interventions and to understand the mechanisms of clinical immunity.


Assuntos
Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Pré-Escolar , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Medição de Risco , Fatores de Risco , Uganda/epidemiologia
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