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1.
BMC Infect Dis ; 23(1): 411, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37328808

RESUMO

BACKGROUND: Historically, malaria has been the predominant cause of acute febrile illness (AFI) in sub-Saharan Africa. However, during the last two decades, malaria incidence has declined due to concerted public health control efforts, including the widespread use of rapid diagnostic tests leading to increased recognition of non-malarial AFI etiologies. Our understanding of non-malarial AFI is limited due to lack of laboratory diagnostic capacity. We aimed to determine the etiology of AFI in three distinct regions of Uganda. METHODS: A prospective clinic-based study that enrolled participants from April 2011 to January 2013 using standard diagnostic tests. Participant recruitment was from St. Paul's Health Centre (HC) IV, Ndejje HC IV, and Adumi HC IV in the western, central and northern regions, which differ by climate, environment, and population density. A Pearson's chi-square test was used to evaluate categorical variables, while a two-sample t-test and Krukalis-Wallis test were used for continuous variables. RESULTS: Of the 1281 participants, 450 (35.1%), 382 (29.8%), and 449 (35.1%) were recruited from the western, central, and northern regions, respectively. The median age (range) was 18 (2-93) years; 717 (56%) of the participants were female. At least one AFI pathogen was identified in 1054 (82.3%) participants; one or more non-malarial AFI pathogens were identified in 894 (69.8%) participants. The non-malarial AFI pathogens identified were chikungunya virus, 716 (55.9%); Spotted Fever Group rickettsia (SFGR), 336 (26.2%) and Typhus Group rickettsia (TGR), 97 (7.6%); typhoid fever (TF), 74 (5.8%); West Nile virus, 7 (0.5%); dengue virus, 10 (0.8%) and leptospirosis, 2 (0.2%) cases. No cases of brucellosis were identified. Malaria was diagnosed either concurrently or alone in 404 (31.5%) and 160 (12.5%) participants, respectively. In 227 (17.7%) participants, no cause of infection was identified. There were statistically significant differences in the occurrence and distribution of TF, TGR and SFGR, with TF and TGR observed more frequently in the western region (p = 0.001; p < 0.001) while SFGR in the northern region (p < 0.001). CONCLUSION: Malaria, arboviral infections, and rickettsioses are major causes of AFI in Uganda. Development of a Multiplexed Point-of-Care test would help identify the etiology of non-malarial AFI in regions with high AFI rates.


Assuntos
Malária , Infecções por Rickettsia , Rickettsia , Febre Tifoide , Humanos , Feminino , Adolescente , Masculino , Estudos Prospectivos , Uganda/epidemiologia , Infecções por Rickettsia/diagnóstico , Febre/epidemiologia , Febre/etiologia , Febre/diagnóstico , Malária/complicações , Malária/epidemiologia , Malária/diagnóstico , Febre Tifoide/complicações
2.
J Antimicrob Chemother ; 76(9): 2407-2414, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-33993252

RESUMO

BACKGROUND: WHO revised their HIV drug resistance (HIVDR) monitoring strategy in 2014, enabling countries to generate nationally representative HIVDR prevalence estimates from surveys conducted using this methodology. In 2016, we adopted this strategy in Uganda and conducted an HIVDR survey among adults initiating or reinitiating ART. METHODS: A cross-sectional survey of adults aged ≥18 years initiating or reinitiating ART was conducted at 23 sites using a two-stage cluster design sampling method. Participants provided written informed consent prior to enrolment. Whole blood collected in EDTA vacutainer tubes was used for preparation of dried blood spot (DBS) specimens or plasma. Samples were shipped from the sites to the Central Public Health Laboratory (CPHL) for temporary storage before transfer to the Uganda Virus Research Institute (UVRI) for genotyping. Prevalence of HIVDR among adults initiating or reinitiating ART was determined. RESULTS: Specimens from 491 participants (median age 32 years and 61.5% female) were collected between August and December 2016. Specimens from 351 participants were successfully genotyped. Forty-nine had drug resistance mutations, yielding an overall weighted HIVDR prevalence of 18.2% with the highest noted for NNRTIs at 14.1%. CONCLUSIONS: We observed a high HIVDR prevalence for NNRTIs among adults prior to initiating or reinitiating ART in Uganda. This is above WHO's recommended threshold of 10% when countries should consider changing from NNRTI- to dolutegravir-based first-line regimens. This recommendation was adopted in the revised Ugandan ART guidelines. Dolutegravir-containing ART regimens are preferred for first- and second-line ART regimens.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Adolescente , Adulto , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , Farmacorresistência Viral , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Uganda/epidemiologia , Carga Viral
3.
J Antimicrob Chemother ; 75(5): 1280-1289, 2020 05 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.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adulto , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , Resistência a Medicamentos , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Prevalência , Falha de Tratamento , Uganda/epidemiologia , Carga Viral
4.
BMC Infect Dis ; 18(1): 93, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-29482500

RESUMO

INTRODUCTION: The World Health Organization recommends that countries conduct two phase evaluations of HIV rapid tests (RTs) in order to come up with the best algorithms. In this report, we present the first ever such evaluation in Uganda, involving both blood and oral based RTs. The role of weak positive (WP) bands on the accuracy of the individual RT and on the algorithms was also investigated. METHODS: In total 11 blood based and 3 oral transudate kits were evaluated. All together 2746 participants from seven sites, covering the four different regions of Uganda participated. Two enzyme immunoassays (EIAs) run in parallel were used as the gold standard. The performance and cost of the different algorithms was calculated, with a pre-determined price cut-off of either cheaper or within 20% price of the current algorithm of Determine + Statpak + Unigold. In the second phase, the three best algorithms selected in phase I were used at the point of care for purposes of quality control using finger stick whole blood. RESULTS: We identified three algorithms; Determine + SD Bioline + Statpak; Determine + Statpak + SD Bioline, both with the same sensitivity and specificity of 99.2% and 99.1% respectively and Determine + Statpak + Insti, with sensitivity and specificity of 99.1% and 99% respectively as having performed better and met the cost requirements. There were 15 other algorithms that performed better than the current one but rated more than the 20% price. None of the 3 oral mucosal transudate kits were suitable for inclusion in an algorithm because of their low sensitivities. Band intensity affected the performance of individual RTs but not the final algorithms. CONCLUSION: We have come up with three algorithms we recommend for public or Government procurement based on accuracy and cost. In case one algorithm is preferred, we recommend to replace Unigold, the current tie breaker with SD Bioline. We further recommend that all the 18 algorithms that have shown better performance than the current one are made available to the private sector where cost may not be a limiting factor.


Assuntos
Infecções por HIV/diagnóstico , HIV-1/isolamento & purificação , Programas de Rastreamento/métodos , Kit de Reagentes para Diagnóstico , Adulto , Algoritmos , Feminino , Infecções por HIV/virologia , Humanos , Técnicas Imunoenzimáticas/métodos , Técnicas Imunoenzimáticas/normas , Masculino , Programas de Rastreamento/normas , Sistemas Automatizados de Assistência Junto ao Leito , Valor Preditivo dos Testes , Kit de Reagentes para Diagnóstico/normas , Sensibilidade e Especificidade , Uganda
5.
BMC Infect Dis ; 18(1): 498, 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30285648

RESUMO

BACKGROUND: Ebolavirus and Marburgvirus are genera of the virus family Filoviridae. Filoviruses cause rare but fatal viral hemorrhagic fevers (VHFs) in remote villages of equatorial Africa with potential for regional and international spread. Point-of-care (POC) rapid diagnostic tests (RDTs) are critical for early epidemic detection, reponse and control. There are 2 RDTs for Zaire ebolavirus (EBOV), but not other Ebolavirus spp. or Marburg marburgvirus (MARV). We validate 3 conserved B cell epitopes of filovirus glycoprotein (GP) using ebola virus diseases (EVD) survivor samples, towards devising pan-filovirus RDTs. METHODS: In-silico Immuno-informatics:- (a) multiple and basic local alignments of amino-acid sequences of filovirus (4 Ebolavirus spp. & MARV) Gp1, 2 and epitope prediction and conservation analyses within context of ClusterW, BLAST-P and the immune epitope database analysis resource (IEDB-AR); alongside (b) in-vitro enzyme immuno-assays (EIAs) for SUDV Gp1, 2 antigen and host-specific antibodies (IgM and IgG) among 94 gamma irradiated EVD survivor serum and 9 negative controls. RESULTS: Linear B cell epitopes were present across the entire length of all Gp1, 2, most lying in the region between amino acids positioned 350 and 500. Three seperate epitopes 97/80_GAFFLYDRLAST, 39_YEAGEWAENCY and 500_CGLRQLANETTQALQLFLRATTELR (designated UG-Filo-Peptide- 1, 2 and 3 respectively) were conserved within all studied filovirus species Gp1, 2. Gp1, 2 host specific IgM levels were comparably low (av. ODs < 0.04 [95% CI: 0.02837 to 0.04033]) among the 9 negative controls and 57 survivor samples analyzed. Host specific IgG levels, on the other hand, were elevated (av. ODs > 1.7525 [95% CI: 0.3010 to 3.1352]) among the 92 survivor samples relative to the 9 negative controls (av. ODs < 0.2.321 [95% CI: -0.7596 to 0.5372]). Filovirus Gp1, 2 antigen was not detected [av. ODs < 0.20] within EVD survivor serum relative to recombinant protein positive controls [av. ODs = 0.50]. CONCLUSIONS: These conserved B cell epitopes of filovirus Gp1, 2 and their derivative antibodies are promising for research and development of RDTs for EVD, with potential for extension to detect MVD.


Assuntos
Ebolavirus/imunologia , Epitopos de Linfócito B/imunologia , Glicoproteínas/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Antivirais/imunologia , Sequência Conservada , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/virologia , Humanos , Imunoglobulina G , Imunoglobulina M , Doença do Vírus de Marburg/diagnóstico , Doença do Vírus de Marburg/virologia , Marburgvirus/imunologia , Kit de Reagentes para Diagnóstico , Proteínas Virais/genética , Proteínas Virais/imunologia
6.
Emerg Infect Dis ; 23(3)2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28125398

RESUMO

The US Food and Drug Administration recently approved ciprofloxacin for treatment of plague (Yersina pestis infection) based on animal studies. Published evidence of efficacy in humans is sparse. We report 5 cases of culture-confirmed human plague treated successfully with oral ciprofloxacin, including 1 case of pneumonic plague.


Assuntos
Antibacterianos/uso terapêutico , Ciprofloxacina/uso terapêutico , Peste/tratamento farmacológico , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peste/epidemiologia , Uganda/epidemiologia
7.
Oncology ; 89(1): 60-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25765812

RESUMO

Fueled by HIV, sub-Saharan Africa has the highest incidence of Kaposi's sarcoma (KS) in the world. Despite this, KS diagnosis in the region is based mostly on clinical grounds. Where biopsy is available, it has traditionally been excisional and performed by surgeons, resulting in multiple appointments, follow-up visits for suture removal, and substantial costs. We hypothesized that a simpler approach - skin punch biopsy - would make histologic diagnosis more accessible. To address this, we provided training and equipment for skin punch biopsy of suspected KS to three HIV clinics in East Africa. The procedure consisted of local anesthesia followed by a disposable cylindrical punch blade to obtain specimens. Hemostasis is facilitated by Gelfoam®. Patients removed the dressing after 4 days. From 2007 to 2013, 2,799 biopsies were performed. Although originally targeted to be used by physicians, biopsies were performed predominantly by nurses (62%), followed by physicians (15%), clinical officers (12%) and technicians (11%). There were no reports of recurrent bleeding or infection. After minimal training and provision of inexpensive equipment (USD 3.06 per biopsy), HIV clinics in East Africa can integrate same-day skin punch biopsy for suspected KS. Task shifting from physician to non-physician greatly increases access. Skin punch biopsy should be part of any HIV clinic's essential procedures. This example of task shifting may also be applicable to the diagnosis of other cancers (e.g., breast) in resource-limited settings.


Assuntos
Biópsia/métodos , Pessoal de Saúde/estatística & dados numéricos , Saúde Pública/métodos , Sarcoma de Kaposi/diagnóstico , Análise e Desempenho de Tarefas , Adulto , África Subsaariana/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Punções , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/patologia , Pele
8.
Trop Med Int Health ; 20(12): 1771-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26391634

RESUMO

Africa is a continent with a large burden of both infectious and non-communicable diseases. If we are to move forward as a continent, we need to equip our growing cadre of exceptional young scientists with the skills needed to tackle the diseases endemic to this continent. For this, immunology is among the key disciplines. Africans should be empowered to study and understand the diseases that affect them, and to perform their cutting-edge research in their country of origin. This requires a multifaceted approach, with buy-in from funders, overseas partners and perhaps, most important of all, African governments themselves.


Assuntos
Alergia e Imunologia , Pesquisa Biomédica , Fortalecimento Institucional , Controle de Doenças Transmissíveis , Doenças Transmissíveis/imunologia , África , Animais , Humanos
9.
PLoS Pathog ; 8(10): e1002877, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23055920

RESUMO

Marburg virus (family Filoviridae) causes sporadic outbreaks of severe hemorrhagic disease in sub-Saharan Africa. Bats have been implicated as likely natural reservoir hosts based most recently on an investigation of cases among miners infected in 2007 at the Kitaka mine, Uganda, which contained a large population of Marburg virus-infected Rousettus aegyptiacus fruit bats. Described here is an ecologic investigation of Python Cave, Uganda, where an American and a Dutch tourist acquired Marburg virus infection in December 2007 and July 2008. More than 40,000 R. aegyptiacus were found in the cave and were the sole bat species present. Between August 2008 and November 2009, 1,622 bats were captured and tested for Marburg virus. Q-RT-PCR analysis of bat liver/spleen tissues indicated ~2.5% of the bats were actively infected, seven of which yielded Marburg virus isolates. Moreover, Q-RT-PCR-positive lung, kidney, colon and reproductive tissues were found, consistent with potential for oral, urine, fecal or sexual transmission. The combined data for R. aegyptiacus tested from Python Cave and Kitaka mine indicate low level horizontal transmission throughout the year. However, Q-RT-PCR data show distinct pulses of virus infection in older juvenile bats (~six months of age) that temporarily coincide with the peak twice-yearly birthing seasons. Retrospective analysis of historical human infections suspected to have been the result of discrete spillover events directly from nature found 83% (54/65) events occurred during these seasonal pulses in virus circulation, perhaps demonstrating periods of increased risk of human infection. The discovery of two tags at Python Cave from bats marked at Kitaka mine, together with the close genetic linkages evident between viruses detected in geographically distant locations, are consistent with R. aegyptiacus bats existing as a large meta-population with associated virus circulation over broad geographic ranges. These findings provide a basis for developing Marburg hemorrhagic fever risk reduction strategies.


Assuntos
Quirópteros/virologia , Doença do Vírus de Marburg/epidemiologia , Doença do Vírus de Marburg/transmissão , Marburgvirus/isolamento & purificação , Animais , Sequência de Bases , Cavernas , Quirópteros/classificação , Reservatórios de Doenças , Feminino , Humanos , Masculino , Marburgvirus/genética , Proteínas Nucleares/genética , Filogenia , RNA Viral/análise , Estudos Retrospectivos , Estações do Ano , Análise de Sequência de RNA , Uganda/epidemiologia , Proteínas Virais Reguladoras e Acessórias/genética
10.
J Med Virol ; 86(10): 1796-803, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24889739

RESUMO

Epstein-Barr virus (EBV) has been linked to malignancies and chronic inflammatory conditions. In this study, EBV detection was compared in children with non-Hodgkin's lymphoma and children with chronic inflammatory conditions, using samples and data from a case-control study carried out at the Mulago National Referral Hospital between 2004 and 2008. EBV viral load was measured in saliva, whole blood and white blood cells by real-time PCR. Serological values for IgG-VCA, EBNA1, and EAd-IgG were compared in non-Hodgkin's lymphoma and chronic inflammatory conditions; and in Burkitt's lymphoma and other subtypes of non-Hodgkin's lymphoma. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Of the 127 children included (87 males and 40 females; median age 7 years, range 2-17), 96 had non-Hodgkin's lymphoma (46 Burkitt's lymphoma and 50 other non-Hodgkin's lymphoma), 31 had chronic inflammatory conditions, and only 10% were HIV-positive. The most common clinical presentations for all disease categories considered were fever, night sweats, and weight loss. EBV viral load in whole blood was elevated in Burkitt's lymphoma compared to other non-Hodgkin's lymphoma (OR 6.67, 95% CI 1.32, 33.69; P-value = 0.04), but EBV viral loads in saliva and white blood cells were not different in any of the disease categories considered. A significant difference in EAd-IgG was observed when non-Hodgkin's lymphoma was compared with chronic inflammatory conditions (OR 0.19, 95% CI 0.07, 0.51; P-value = 0.001). When compared to chronic inflammatory conditions, EBV viral load was elevated in Burkitt's lymphoma, and EA IgG was higher in non-Hodgkin's lymphoma. This study supports an association between virological and serological markers of EBV and childhood non-Hodgkin's lymphoma, irrespective of subtype, in Uganda.


Assuntos
Infecções por Vírus Epstein-Barr/epidemiologia , Herpesvirus Humano 4/isolamento & purificação , Inflamação/virologia , Linfoma não Hodgkin/virologia , Carga Viral , Adolescente , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Sangue/virologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Doença Crônica , Feminino , Humanos , Imunoglobulina G/sangue , Leucócitos/virologia , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Saliva/virologia , Estudos Soroepidemiológicos , Uganda/epidemiologia
11.
Emerg Infect Dis ; 18(9): 1480-3, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22931687

RESUMO

Two large outbreaks of Ebola hemorrhagic fever occurred in Uganda in 2000 and 2007. In May 2011, we identified a single case of Sudan Ebola virus disease in Luwero District. The establishment of a permanent in-country laboratory and cooperation between international public health entities facilitated rapid outbreak response and control activities.


Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Surtos de Doenças , Ebolavirus/genética , Doença pelo Vírus Ebola/epidemiologia , Criança , Doenças Transmissíveis Emergentes/diagnóstico , Ebolavirus/classificação , Ebolavirus/isolamento & purificação , Monitoramento Epidemiológico , Evolução Fatal , Feminino , Doença pelo Vírus Ebola/diagnóstico , Humanos , Uganda/epidemiologia
12.
Afr Health Sci ; 22(Spec Issue): 1-10, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36321127

RESUMO

The Infectious Diseases Institute (IDI), established in 2001, was the first autonomous institution of Makerere University set up as an example of what self-governing institutes can do in transforming the academic environment to become a rapidly progressive University addressing the needs of society This paper describes the success factors and lessons learned in development of sustainable centers of excellence to prepare academic institutions to respond appropriately to current and future challenges to global health. Key success factors included a) strong collaboration by local and international experts to combat the HIV pandemic, along with b) seed funding from Pfizer Inc., c) longstanding collaboration with Accordia Global Health Foundation to create and sustain institutional strengthening programs, d) development of a critical mass of multi-disciplinary research leaders and managers of the center, and e) a series of strong directors who built strong governance structures to execute the vision of the institute, with subsequent transition to local leadership. Conclusion: Twenty years of sustained investment in infrastructure, human capital, leadership, and collaborations present Makerere University and the sub-Saharan Africa region with an agile center of excellence with preparedness to meet the current and future challenges to global health.


Assuntos
Fortalecimento Institucional , Doenças Transmissíveis , Humanos , Universidades , Cooperação Internacional , Atenção à Saúde
14.
PLoS Pathog ; 5(7): e1000536, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19649327

RESUMO

In July and September 2007, miners working in Kitaka Cave, Uganda, were diagnosed with Marburg hemorrhagic fever. The likely source of infection in the cave was Egyptian fruit bats (Rousettus aegyptiacus) based on detection of Marburg virus RNA in 31/611 (5.1%) bats, virus-specific antibody in bat sera, and isolation of genetically diverse virus from bat tissues. The virus isolates were collected nine months apart, demonstrating long-term virus circulation. The bat colony was estimated to be over 100,000 animals using mark and re-capture methods, predicting the presence of over 5,000 virus-infected bats. The genetically diverse virus genome sequences from bats and miners closely matched. These data indicate common Egyptian fruit bats can represent a major natural reservoir and source of Marburg virus with potential for spillover into humans.


Assuntos
Quirópteros/virologia , Doença do Vírus de Marburg/virologia , Marburgvirus/genética , Animais , Anticorpos Antivirais/sangue , Antígenos Virais/sangue , Quirópteros/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Fígado/química , Fígado/virologia , Masculino , Doença do Vírus de Marburg/sangue , Marburgvirus/isolamento & purificação , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Uganda
15.
Biomarkers ; 16(1): 42-50, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20979563

RESUMO

A single-nucleotide polymorphism in the MDM2 promoter (SNP309; rs2279744) causes elevated transcription of this major negative regulator of p53 in several cancer types. We investigated MDM2 SNP309 and CDKN1A (p21/Waf1/Cip1) codon 31 (rs1801270) polymorphisms in 86 cases of cutaneous Kaposi's sarcoma (KS) from African and Caucasian patients, and 210 healthy controls. A significant increase of the MDM2 SNP309 T/G genotype was observed among classic KS cases (odds ratio 2.38, 95% confidence interval 1.0-5.5). Frequencies of CDKN1A codon 31 genotypes were not significantly different between cases and controls. The results suggest that the MDM2 SNP309 G allele may act as a susceptibility gene for the development of classic KS in Caucasian patients.


Assuntos
População Negra/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Sarcoma de Kaposi/genética , População Branca/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sarcoma de Kaposi/diagnóstico , Proteína Supressora de Tumor p53/genética , Adulto Jovem
16.
Artigo em Inglês | MEDLINE | ID: mdl-33216708

RESUMO

Aflatoxins are carcinogenic mycotoxins that contaminate a variety of crops worldwide. Acute exposure can cause liver failure, and chronic exposure can lead to stunting in children and liver cancer in adults. We estimated aflatoxin exposure across Uganda by measuring a serum biomarker of aflatoxin exposure in a subsample from the 2011 Uganda AIDS Indicator Survey, a nationally representative survey of HIV prevalence, and examined its association with geographic, demographic, and socioeconomic variables. We analysed a subsample of 985 serum specimens selected among HIV-negative participants from 10 survey-defined geographic regions for serum aflatoxin B1-lysine (AFB1-lys) by use of isotope dilution LC-MS/MS and calculated results normalised to serum albumin. We used statistical techniques for censored data to estimate geometric means (GMs), standard deviations, and percentiles. We detected serum AFB1-lys in 71.7% of specimens (LOD = 0.5 pg/mg albumin). Unadjusted GM AFB1-lys (pg/mg albumin) was 1.33 (95% CI: 1.21-1.47). Serum AFB1-lys was higher in males (GM: 1.57; 95% CI: 1.38-1.80) vs. females (GM: 1.12; 95% CI: 0.97-1.30) (P = .0019), and higher in persons residing in urban settings (GM: 2.83; 95% CI: 2.37-3.37) vs. rural (GM: 1.10; 95% CI: 0.99-1.23) (P < .0001). When we used a multivariable censored regression model to assess confounding and interactions among variables we found that survey region, gender, age, occupation, distance to marketplace, and number of meals per day were statistically significant predictors of aflatoxin exposure. While not nationally representative, our findings provide an improved understanding of the widespread burden of aflatoxin exposure throughout Uganda and identify key geographic, demographic, and socioeconomic factors that may modulate aflatoxin exposure risk.


Assuntos
Síndrome da Imunodeficiência Adquirida/sangue , Aflatoxina B1/sangue , Coleta de Amostras Sanguíneas , Exposição Ambiental/análise , Inquéritos Epidemiológicos , Adolescente , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Emerg Infect Dis ; 16(5): 866-8, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20409387

RESUMO

After recreational exposure to river water in Uganda, 12 (17%) of 69 persons had evidence of schistosome infection. Eighteen percent self-medicated with praziquantel prophylaxis immediately after exposure, which was not appropriate. Travelers to schistosomiasis-endemic areas should consult a travel medicine physician.


Assuntos
Recreação , Rios , Esquistossomose/epidemiologia , Adolescente , Adulto , Idoso , Animais , Anti-Helmínticos/administração & dosagem , Anticorpos Anti-Helmínticos/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Profilaxia Pós-Exposição , Praziquantel/administração & dosagem , Schistosoma/imunologia , Esquistossomose/etiologia , Esquistossomose/prevenção & controle , Automedicação , Medicina de Viagem , Uganda/epidemiologia
18.
Scand J Infect Dis ; 42(6-7): 522-6, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20180681

RESUMO

Although infections with multiple human papillomavirus (HPV) types have been reported widely, more information is needed on the occurrence of the different types. We determined the distribution of seroprevalences to multiple HPV types in Finland and Uganda to compare the epidemiology of the different HPV types in the 2 populations. Serum samples were obtained from 2784 Finnish and 1964 Ugandan women (mean ages 22 y and 25 y, respectively) of whom 44% and 57%, respectively, had antibodies to at least 1 of the 7 HPV types (6, 11, 16, 18, 31, 33, 45) tested (p < 0.001). Multiple HPV antibody positivity was common. HPV45-seropositive Finns had a higher risk of having antibodies to other high-risk HPV types: HPV18 (odds ratio (OR) = 10.9), HPV31 (OR 6.1), HPV33 (OR 12.2), than their Ugandan counterparts: HPV18 (OR 3.4), HPV31 (OR 2.2), HPV33 (OR 3.3). Increased estimates for being double antibody-positive were also noted among HPV18- and HPV16-seropositive women, but there were no major differences between HPV16-seropositive Finns and Ugandans. In addition to biological and behavioural factors, iatrogenic and societal factors (screening vs no screening) may also result in the different occurrence of infections with the high-risk HPV types in Finland and Uganda.


Assuntos
Alphapapillomavirus/classificação , Infecções por Papillomavirus/epidemiologia , Adolescente , Adulto , Alphapapillomavirus/isolamento & purificação , Anticorpos Antivirais/sangue , Feminino , Finlândia/epidemiologia , Soropositividade para HIV , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , Infecções por Papillomavirus/virologia , Fatores de Risco , Estudos Soroepidemiológicos , Uganda/epidemiologia
19.
PLoS One ; 15(4): e0230451, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32287264

RESUMO

INTRODUCTION: With the scale-up of antiretroviral therapy (ART) there is a need to monitor programme performance to maximize ART efficacy and to prevent emergence of HIV drug resistance (HIVDR). In keeping with the elements of the World Health Organisation (WHO) guidance we carried out a nationally representative assessment of early warning indicators (EWI) at 304 randomly selected ART service outlets in Uganda. METHODS: Retrospective patient data was extracted for the six EWIs for HIVDR including; on-time antiretroviral (ARV) drug pick-up, patient retention on ART at 12 months, ART dispensing practices, ARV drug stock-outs, viral load suppression (VLS) and viral load (VL) testing completion. Point prevalence for each clinic and national aggregate prevalence with 95% confidence intervals (CI) for all clinics were estimated and facility performances were computed and association between EWIs and programmatic factors assessed using Fisher's Exact Test. RESULTS: Facilities meeting the EWI targets: on-time pill pick-up was 9.5%, more facilities in the north met this target (p = 0.040). Retention on ART at 12 months was 24.1%, facilities in Kampala region (p<0.001) and Specialized ART clinics (p = 0.01) performed better in this indicator. Pharmacy stock-outs was 33.6%, with more facilities in Kampala (p<0.001), specialized ART clinics (p<0.001) and private-for-profit (p<0.001) meeting this target. Dispensing practices was met by 100% of the facilities. VLS was met by 49.2% and 50.8% of facilities met VL completion target with facilities in central region performing better (p<0.001). National prevalence for the EWIs was: on-time pill pick-up 63.3% (CI: 58.9-67.8); retention on ART at 12 months 69.9% (CI: 63.8-76.0); dispensing practices 100.0%; VLS 85.2% (CI: 81.8-88.5) and VL completion, 60.7% (CI: 56.9-64.6). CONCLUSION: Dispensing practices in all facilities were in line with the national guidelines however, there still remains a challenge to long-term ART programmatic success in monitoring patient response to treatment, and maintaining patients on ART without interruptions arising due to poor patient adherence and as a consequence of ARV supply interruption. It is therefore of high importance that the national ART program ensures intensified follow-up for patients, ensuring uninterrupted supply of ARV drugs and increasing VL monitoring at treatment centres, in order to improve patient outcomes and avert preventable HIVDR.


Assuntos
Antirretrovirais/provisão & distribuição , Infecções por HIV/tratamento farmacológico , Cooperação do Paciente/estatística & dados numéricos , Adulto , Antirretrovirais/uso terapêutico , Farmacorresistência Viral , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Prevalência , Estudos Retrospectivos , Inquéritos e Questionários , Uganda , Carga Viral , Organização Mundial da Saúde
20.
J Oncol ; 2020: 3254820, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32280342

RESUMO

BACKGROUND: Despite its hallmark cutaneous presentation, most Kaposi's sarcoma (KS) in Africa is diagnosed too late for effective treatment. Early diagnosis will only be achievable if patients with KS present earlier for care. We hypothesized that public awareness about KS can be enhanced through exposure to common media. METHODS: We developed educational messages regarding early detection of KS for the general African public portraying a three-part theme: "Look" (regularly examine one's skin/mouth), "Show" (bring to the attention of a healthcare provider any skin/mouth changes), and "Test" (ask for a biopsy for definitive diagnosis). We packaged the messages in three common media forms (comic strips, radio, and video) and tested their effect on increasing KS awareness among adults attending markets in Uganda. Participants were randomized to a single exposure to one of the media and evaluated for change in KS-related knowledge and attitudes. RESULTS: Among 420 participants, media exposure resulted in increased ability to identify KS (from 0.95% pretest to 46% posttest); awareness that anyone is at risk for KS (29% to 50%); belief that they may be at risk (63% to 76%); and knowledge that definitive diagnosis requires biopsy (23% to 51%) (all p < 0.001). Most participants (96%) found the media culturally appropriate. CONCLUSION: Exposure to media featuring a theme of "Look," "Show," and "Test" resulted in changes in knowledge and attitudes concerning KS among the general public in Uganda. High incidence and poor survival of KS in Africa are an impetus to further evaluate these media, which are freely available online.

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