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1.
Emerg Infect Dis ; 30(10): 2128-2134, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39213261

RESUMEN

We linked 4 mpox cases in South Ubangi, Democratic Republic of the Congo, to transboundary transmission from Central African Republic. Viral genome sequencing demonstrated that the monkeypox virus sequences belonged to distinct clusters of subclade Ia. This finding demonstrates the borderless nature of mpox and highlights the need for vigilant regional surveillance.


Asunto(s)
Monkeypox virus , Mpox , Filogenia , Monkeypox virus/genética , Monkeypox virus/clasificación , República Democrática del Congo/epidemiología , Mpox/epidemiología , Mpox/virología , Mpox/transmisión , Humanos , República Centroafricana/epidemiología , Masculino , Genoma Viral , Femenino , Adulto , Persona de Mediana Edad
2.
BMC Pregnancy Childbirth ; 24(1): 556, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39192226

RESUMEN

BACKGROUND: Deaths occurring during the neonatal period contribute close to half of under-five mortality rate (U5MR); over 80% of these deaths occur in low- and middle-income countries (LMICs). Poor maternal antepartum and perinatal health predisposes newborns to low birth weight (LBW), birth asphyxia, and infections which increase the newborn's risk of death. METHODS: The objective of the study was to assess the association between abnormal postpartum maternal temperature and early infant outcomes, specifically illness requiring hospitalisation or leading to death between birth and six weeks' age. We prospectively studied a cohort of neonates born at Mbarara Regional Referral Hospital in Uganda to mothers with abnormal postpartum temperature and followed them longitudinally through early infancy. We performed a logistic regression of the relationship between maternal abnormal temperature and six-week infant hospitalization, adjusting for gestational age and 10-minute APGAR score at birth. RESULTS: Of the 648 postpartum participants from the parent study who agreed to enrol their neonates in the sub-study, 100 (15%) mothers had abnormal temperature. The mean maternal age was 24.6 (SD 5.3) years, and the mean parity was 2.3 (SD 1.5). There were more preterm babies born to mothers with abnormal maternal temperature (10%) compared to 1.1% to mothers with normal temperature (p=˂0.001). While the majority of newborns (92%) had a 10-minute APGAR score > 7, 14% of newborns whose mothers had abnormal temperatures had APGAR score ˂7 compared to 7% of those born to mothers with normal postpartum temperatures (P = 0.02). Six-week outcome data was available for 545 women and their infants. In the logistic regression model adjusted for gestational age at birth and 10-minute APGAR score, maternal abnormal temperature was not significantly associated with the composite adverse infant health outcome (being unwell or dead) between birth and six weeks' age (aOR = 0.35, 95% CI 0.07-1.79, P = 0.21). The 10-minute APGAR score was significantly associated with adverse six-week outcome (P < 0.01). CONCLUSIONS: While our results do not demonstrate an association between abnormal maternal temperature and newborn and early infant outcomes, good routine neonate care should be emphasized, and the infants should be observed for any abnormal findings that may warrant further assessment. TARGET JOURNAL: BMC Pregnancy and Childbirth ( https://bmcpregnancychildbirth.biomedcentral.com/ ).


Asunto(s)
Hipotermia , Mortalidad Infantil , Humanos , Uganda/epidemiología , Femenino , Recién Nacido , Hipotermia/mortalidad , Embarazo , Adulto , Lactante , Estudios Prospectivos , Hipertermia , Adulto Joven , Puntaje de Apgar , Periodo Posparto , Enfermedades del Recién Nacido/mortalidad , Enfermedades del Recién Nacido/epidemiología , Masculino , Recién Nacido de Bajo Peso , Edad Gestacional , Modelos Logísticos , Recien Nacido Prematuro
3.
Emerg Infect Dis ; 29(9): 1846-1849, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37437563

RESUMEN

During 2016-2022, PCR testing confirmed 100 mpox cases among 302 suspected cases in the Central African Republic. The highest detection rates were from active lesions (40%) and scabs (36%); cycle thresholds were lower (≈18) than those for blood samples (≈33). Results were consistent for generic primer- and clade I primer-specific PCR tests.


Asunto(s)
Mpox , Humanos , República Centroafricana/epidemiología , Técnicas de Laboratorio Clínico
4.
HIV Med ; 24(6): 691-702, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36717222

RESUMEN

BACKGROUND: With the success of antiretroviral therapy (ART), children born with HIV are more likely to reach adolescence. However, frequent non-adherence to ART in adolescents living with HIV (ALHIV) leads to viral replication. Notably, a viraemic infection might lead to archived drug resistance mutations (ADRMs). Hence, within the context of the COVID-19 pandemic, we aimed to compare the patterns of ADRMs in viraemic and non-viraemic vertically infected ALHIV and to assess their immunity to and diagnosis of SARS-CoV-2. METHODS: A comparative study was conducted among COVID-19-unvaccinated ALHIV receiving ART in Yaoundé-Cameroon over the period October 2021 to March 2022. Plasma HIV-RNA was measured using Abbott® m2000rt; HIV-1 genotyping was performed on buffy-coat (HIV-1 DNA) and ADRMs were interpreted using HIVdb.v9.0.1. Patterns of HIV-1 ADRMs were compared between viraemic (≥ 1.60 log10 HIV-1 RNA copies/ml) and non-viraemic (< 1.60 log10 copies/ml) individuals. SARS-CoV-2 antibodies were assessed on whole blood using Abbott Panbio COVID-19 immunoglobulin G/M (IgG/IgM) rapid test and COVID-19 polymerase chain reaction test was performed using nasopharyngeal swab samples. RESULTS: Of the 60 ALHIV [aged 17 (16-19) years, 51.6% female], median ART duration was 14 (12-16) years; 31/55 (56.3%) were exposed to nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART (of whom 19/31 transitioned to dolutegravir-based ART in 2020) and 24/55 (43.6%) were on second-line ART. Forty-two out of 60 (70.0%) ALHIV were non-viraemic; 43/60 (71.6%) were successfully sequenced. Overall the ADRM rate was 62.7% (27/43), with 69.2% (9/13) viraemic and 60.0% (18/30) non-viraemic (p = 0.56). NNRTI-ADRMs were significantly higher among viraemic ALHIV (69.2% vs. 46.7%, p = 0.030). Regarding immunity, those with CD4 nadir < 350 cells/µl had significantly higher rates of ADRMs [adjusted odds ratio (aOR) = 3.20 (1.36-95.53), p = 0.03]. In relation to COVID-19 immunity, overall SARS-CoV-2 IgG seropositivity was 28.3% (17/60), whereas 0% (0/60) were seropositive to IgM; in particular, those with CD4 count nadir ≥ 350 cells/µl had higher odds of SARS-CoV-2 IgG seropositivity [OR =7.85 (2.03-30.28), p < 0.01]. No significant association was found between SARS-CoV-2 IgG seropositivity and HIV-RNA (non-viraemic, 33.3%; viraemic, 16.7%; p = 0.18). SARS-CoV-2 RNA prevalence was 4.5% (2/44). The two positive participants were with low-levels of viral load (Ct > 30) and seropositive to IgG. CONCLUSION: In the context of virological success, the majority of ALHIV harbour ADRMs, essentially driven by NNRTI mutations and low CD4 nadir. During the current pandemic, about one-third of ALHIV were previously exposed to SARS-CoV-2. However, some children might have been exposed and uninfected and others might have been infected but showed no serological response at sampling. These findings support the use of NNRTI-sparing regimens and the implementation of COVID-19 barrier measures targeting ALHIV during such a pandemic.


Asunto(s)
Fármacos Anti-VIH , COVID-19 , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Niño , Humanos , Femenino , Adolescente , Masculino , VIH-1/genética , Infecciones por VIH/epidemiología , Pandemias , ARN Viral , Camerún/epidemiología , Farmacorresistencia Viral/genética , COVID-19/epidemiología , SARS-CoV-2 , Antirretrovirales/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Mutación , Seropositividad para VIH/tratamiento farmacológico , ADN/uso terapéutico , Carga Viral , Fármacos Anti-VIH/uso terapéutico
5.
Bull World Health Organ ; 101(3): 170-178, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36865607

RESUMEN

Objective: To describe the implementation of case-area targeted interventions to reduce cholera transmission using a rapid, localized response in Kribi district, Cameroon. Methods: We used a cross-sectional design to study the implementation of case-area targeted interventions. We initiated interventions after rapid diagnostic test confirmation of a case of cholera. We targeted households within a 100-250 metre perimeter around the index case (spatial targeting). The interventions package included: health promotion, oral cholera vaccination, antibiotic chemoprophylaxis for nonimmunized direct contacts, point-of-use water treatment and active case-finding. Findings: We implemented eight targeted intervention packages in four health areas of Kribi between 17 September 2020 and 16 October 2020. We visited 1533 households (range: 7-544 per case-area) hosting 5877 individuals (range: 7-1687 per case-area). The average time from detection of the index case to implementation of interventions was 3.4 days (range: 1-7). Oral cholera vaccination increased overall immunization coverage in Kribi from 49.2% (2771/5621 people) to 79.3% (4456/5621 people). Interventions also led to the detection and prompt management of eight suspected cases of cholera, five of whom had severe dehydration. Stool culture was positive for Vibrio cholerae O1 in four cases. The average time from onset of symptoms to admission of a person with cholera to a health facility was 1.2 days. Conclusion: Despite challenges, we successfully implemented targeted interventions at the tail-end of a cholera epidemic, after which no further cases were reported in Kribi up until week 49 of 2021. The effectiveness of case-area targeted interventions in stopping or reducing cholera transmission needs further investigation.


Asunto(s)
Cólera , Humanos , Cólera/epidemiología , Cólera/prevención & control , Camerún/epidemiología , Estudios Transversales , Antibacterianos , Quimioprevención
7.
Malar J ; 21(1): 298, 2022 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-36273147

RESUMEN

BACKGROUND: Urban malaria has received insufficient attention in the literature. The prevalence and clinical characteristics of Plasmodium falciparum infection amongst patients presenting with suspected malaria were investigated at a major urban hospital in Douala, Cameroon with a particular focus on anaemia. METHODS: A cross-sectional, 18-week demographic and clinical survey was conducted of patients presenting to the Emergency Department of Douala Military Hospital with suspected malaria, largely defined by the presence or recent history of fever. Venous samples were tested for P. falciparum using rapid diagnostic tests and PCR, and anaemia was defined by haemoglobin level according to WHO definitions. Likelihood ratios (LR), odds ratios (OR), and population attributable risk percent (PARP) were calculated. RESULTS: Participants were ages 8 months to 86 years, 51% were women (257/503), and all districts of Douala were represented. Overall, 38.0% (n = 189/497) were anaemic, including 5.2% (n = 26/497) with severe anaemia. Anaemia prevalence was significantly higher (OR: 2.20, 95% CI 1.41-3.45) among children < 15 years (53.1%, n = 52/98) compared to adults (34%, n = 133/392). Plasmodium falciparum was detected in 37.2% by nested PCR. Among all participants, several factors were associated with clinically significant LR for P. falciparum infection, including age 10-14 years (positive LR: 3.73), living in the island district of Douala VI (positive LR: 3.41), travel to any of three northern regions (positive LR: 5.11), and high fever > 40 °C at presentation (positive LR: 4.83). Among all participants, 8.7% of anaemia was associated with P. falciparum infection, while the PARP was 33.2% among those < 15 years of age and 81.0% among 10-14-year-olds. CONCLUSIONS: The prevalence of P. falciparum infection in the urban hospital was high. Mirroring trends in many rural African settings, older children had the highest positivity rate for P. falciparum infection. Anaemia was also common in all age groups, and for those 10-14 years of age, 80% of the risk for anaemia was associated with P. falciparum infection. Malaria rates in major urban population centres can be high, and more research into the multifactorial causes of anaemia across the age spectrum are needed.


Asunto(s)
Anemia , Malaria Falciparum , Malaria , Niño , Adulto , Estados Unidos , Humanos , Femenino , Adolescente , Anciano de 80 o más Años , Masculino , Plasmodium falciparum , Estudios Transversales , Hospitales Militares , Camerún/epidemiología , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Malaria Falciparum/diagnóstico , Anemia/etiología , Malaria/complicaciones , Prevalencia , Hemoglobinas/análisis , Hospitales Urbanos
9.
Compr Psychiatry ; 113: 152293, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34959002

RESUMEN

BACKGROUND: Displacement and conflict exposure are known risk factors for mental health conditions. Here, we examine the mental health of youth in a conflict-affected region of Cameroon. METHODS: Participants were recruited from among beneficiaries of a project conducted by Univers Psy and the United Nations Population Fund in Cameroon's Far North region. Community health workers conducted sensitization campaigns, following which they referred adolescents and young adults who self-identified as having mental health concerns to clinical psychologists. We ultimately conducted chart reviews of 948 of these youth. Univariate analyses using chi-squared tests were used to assess the relationships among demographics, displacement status, and mental health. Logistic regressions were then performed to determine the odds of having a psychiatric disorder based on displacement status. OUTCOME: Sixty-eight percent of evaluated youth met criteria for a psychiatric disorder. Anxiety disorders were most prevalent at 24.3%, followed by trauma- and stressor-related disorders at 17.0%, and mood disorders at 8.0%. Refugees and IDPs had 0.11 (95% CI 0.06, 0.19) and 0.46 (95% CI 0.29, 0.74) odds, respectively, of any diagnosis compared to the host population. Females had 1.71 (95% CI 1.17, 2.50) odds of an anxiety disorder and 2.18 (95% CI 1.16, 4.10) odds of a mood disorder compared to males. INTERPRETATION: In a youth sample in Cameroon self-identified as having mental health concerns, this study found high rates of psychiatric illness, particularly anxiety disorders. We found a higher prevalence among host population individuals than among displaced individuals and especially in the female population.


Asunto(s)
Trastornos Mentales , Servicios de Salud Mental , Refugiados , Trastornos por Estrés Postraumático , Adolescente , Camerún/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , Salud Mental , Violencia , Adulto Joven
11.
Malar J ; 20(1): 114, 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33632242

RESUMEN

BACKGROUND: Chloroquine (CQ) resistance is conferred by mutations in the Plasmodium falciparum CQ resistance transporter (pfcrt). Following CQ withdrawal for anti-malarial treatment, studies across malaria-endemic countries have shown a range of responses. In some areas, CQ sensitive parasites re-emerge, and in others, mutant haplotypes persist. Active surveillance of resistance mutations in clinical parasites is essential to inform treatment regimens; this effort requires fast, reliable, and cost-effective methods that work on a variety of sample types with reagents accessible in malaria-endemic countries. METHODS: Quantitative PCR followed by High-Resolution Melt (HRM) analysis was performed in a field setting to assess pfcrt mutations in two groups of clinical samples from Southwestern Uganda. Group 1 samples (119 in total) were collected in 2010 as predominantly Giemsa-stained slides; Group 2 samples (125 in total) were collected in 2015 as blood spots on filter paper. The Rotor-Gene Q instrument was utilized to assess the impact of different PCR-HRM reagent mixes and the detection of mixed haplotypes present in the clinical samples. Finally, the prevalence of the wild type (CVMNK) and resistant pfcrt haplotypes (CVIET and SVMNT) was evaluated in this understudied Southwestern region of Uganda. RESULTS: The sample source (i.e. Giemsa-stained slides or blood spots) and type of LCGreen-based reagent mixes did not impact the success of PCR-HRM. The detection limit of 10- 5 ng and the ability to identify mixed haplotypes as low as 10 % was similar to other HRM platforms. The CVIET haplotype predominated in the clinical samples (66 %, 162/244); however, there was a large regional variation between the sample groups (94 % CVIET in Group 1 and 44 % CVIET in Group 2). CONCLUSIONS: The HRM-based method exhibits the flexibility required to conduct reliable assessment of resistance alleles from various sample types generated during the clinical management of malaria. Large regional variations in CQ resistance haplotypes across Southwestern Uganda emphasizes the need for continued local parasite genotype assessment to inform anti-malarial treatment policies.


Asunto(s)
Antimaláricos/farmacología , Haplotipos , Malaria Falciparum/prevención & control , Proteínas de Transporte de Membrana/genética , Plasmodium falciparum/genética , Proteínas Protozoarias/genética , Preescolar , Resistencia a Medicamentos/genética , Genotipo , Humanos , Lactante , Desnaturalización de Ácido Nucleico , Plasmodium falciparum/efectos de los fármacos , Uganda
13.
PLoS Med ; 17(5): e1003084, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32407380

RESUMEN

BACKGROUND: The radical cure of Plasmodium vivax and P. ovale requires treatment with primaquine or tafenoquine to clear dormant liver stages. Either drug can induce haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, necessitating screening. The reference diagnostic method for G6PD activity is ultraviolet (UV) spectrophotometry; however, a universal G6PD activity threshold above which these drugs can be safely administered is not yet defined. Our study aimed to quantify assay-based variation in G6PD spectrophotometry and to explore the diagnostic implications of applying a universal threshold. METHODS AND FINDINGS: Individual-level data were pooled from studies that used G6PD spectrophotometry. Studies were identified via PubMed search (25 April 2018) and unpublished contributions from contacted authors (PROSPERO: CRD42019121414). Studies were excluded if they assessed only individuals with known haematological conditions, were family studies, or had insufficient details. Studies of malaria patients were included but analysed separately. Included studies were assessed for risk of bias using an adapted form of the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Repeatability and intra- and interlaboratory variability in G6PD activity measurements were compared between studies and pooled across the dataset. A universal threshold for G6PD deficiency was derived, and its diagnostic performance was compared to site-specific thresholds. Study participants (n = 15,811) were aged between 0 and 86 years, and 44.4% (7,083) were women. Median (range) activity of G6PD normal (G6PDn) control samples was 10.0 U/g Hb (6.3-14.0) for the Trinity assay and 8.3 U/g Hb (6.8-15.6) for the Randox assay. G6PD activity distributions varied significantly between studies. For the 13 studies that used the Trinity assay, the adjusted male median (AMM; a standardised metric of 100% G6PD activity) varied from 5.7 to 12.6 U/g Hb (p < 0.001). Assay precision varied between laboratories, as assessed by variance in control measurements (from 0.1 to 1.5 U/g Hb; p < 0.001) and study-wise mean coefficient of variation (CV) of replicate measures (from 1.6% to 14.9%; p < 0.001). A universal threshold of 100% G6PD activity was defined as 9.4 U/g Hb, yielding diagnostic thresholds of 6.6 U/g Hb (70% activity) and 2.8 U/g Hb (30% activity). These thresholds diagnosed individuals with less than 30% G6PD activity with study-wise sensitivity from 89% (95% CI: 81%-94%) to 100% (95% CI: 96%-100%) and specificity from 96% (95% CI: 89%-99%) to 100% (100%-100%). However, when considering intermediate deficiency (<70% G6PD activity), sensitivity fell to a minimum of 64% (95% CI: 52%-75%) and specificity to 35% (95% CI: 24%-46%). Our ability to identify underlying factors associated with study-level heterogeneity was limited by the lack of availability of covariate data and diverse study contexts and methodologies. CONCLUSIONS: Our findings indicate that there is substantial variation in G6PD measurements by spectrophotometry between sites. This is likely due to variability in laboratory methods, with possible contribution of unmeasured population factors. While an assay-specific, universal quantitative threshold offers robust diagnosis at the 30% level, inter-study variability impedes performance of universal thresholds at the 70% level. Caution is advised in comparing findings based on absolute G6PD activity measurements across studies. Novel handheld quantitative G6PD diagnostics may allow greater standardisation in the future.


Asunto(s)
Deficiencia de Glucosafosfato Deshidrogenasa/diagnóstico , Deficiencia de Glucosafosfato Deshidrogenasa/metabolismo , Glucosafosfato Deshidrogenasa/metabolismo , Espectrofotometría , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antimaláricos/uso terapéutico , Niño , Preescolar , Femenino , Deficiencia de Glucosafosfato Deshidrogenasa/tratamiento farmacológico , Humanos , Lactante , Recién Nacido , Malaria/epidemiología , Masculino , Persona de Mediana Edad , Adulto Joven
14.
BMC Pregnancy Childbirth ; 20(1): 385, 2020 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-32616037

RESUMEN

BACKGROUND: While congenital syphilis is a significant public health problem that can cause severe disabilities, little is known about the situation in Uganda. We describe prevalence, associated factors and clinical presentation of congenital syphilis in Mbarara, Uganda. METHODS: A cross sectional study was carried out among mother- newborn dyads from the postnatal ward of Mbarara Regional Referral Hospital (MRRH). After obtaining informed consent, a structured questionnaire was used to capture data on risk factors for congenital syphilis. A finger prick was performed on the mothers for Treponema Pallidum Haemagglutination Assay (TPHA). If TPHA was positive, a venous blood sample was collected from the mother to confirm active infection using Rapid Plasma Reagin (RPR). Venous blood was drawn from a newborn if the mother tested positive by TPHA and RPR. A newborn with RPR titres 4 times higher than the mother was considered to have congenital syphilis. We fit logistic regression models to determine factors associated with congenital syphilis. RESULTS: Between June and September 2015, we enrolled 2500 mothers and 2502 newborns. Prevalence of syphilis was 3.8% (95% CI 3.1-4.6) among newborn infants and 4.1% (95% CI 3.4-5.0) among their mothers. Maternal age <25 years, past history of genital ulcer, a past history of abnormal vaginal discharge, and not receiving treatment of at least one of genital ulcer, genital itching, lower abdominal pain and abnormal vaginal discharge in the current pregnancy were the risk factors associated with congenital syphilis. The most common clinical feature was hepatosplenomegaly. CONCLUSIONS: We found higher-than-expected syphilis sero-prevalence rates in a high risk population of postnatal mothers and their newborns in Uganda. Bridge populations for syphilis may include mothers not tested during pregnancy, who are usually married and not treated. In accordance with our results, the national policy for syphilis control in Uganda should be strengthened to include universal syphilis screening amongst mother-newborn pairs in postnatal clinics with subsequent partner notification.


Asunto(s)
Sífilis Congénita/epidemiología , Adolescente , Adulto , Estudios Transversales , Femenino , Pruebas de Hemaglutinación , Humanos , Recién Nacido , Tamizaje Masivo , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Prevalencia , Sífilis/epidemiología , Serodiagnóstico de la Sífilis , Uganda/epidemiología , Adulto Joven
15.
N Engl J Med ; 374(25): 2453-64, 2016 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-27332904

RESUMEN

BACKGROUND: Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale. METHODS: We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci. RESULTS: We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay. CONCLUSIONS: No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).


Asunto(s)
Artemisininas/farmacología , Resistencia a Medicamentos/genética , Lactonas/farmacología , Mutación , Plasmodium falciparum/genética , Polimorfismo Genético , Proteínas Protozoarias/genética , Algoritmos , Artemisininas/uso terapéutico , Asia Sudoriental , China , Enfermedades Endémicas , Genotipo , Humanos , Lactonas/uso terapéutico , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/parasitología , Plasmodium falciparum/efectos de los fármacos , Análisis de Secuencia de ADN
16.
Ann Intern Med ; 169(3): 146-155, 2018 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-29946683

RESUMEN

Background: Evidence regarding potential adverse neuropsychiatric effects of efavirenz is conflicting, and data from sub-Saharan Africa, where 70% of persons living with HIV (PLHIV) reside and efavirenz is used as first-line therapy, are limited. Objective: To estimate associations between efavirenz use and depression and suicidal ideation among PLHIV in Uganda. Design: Prospective observational cohort study. (ClinicalTrials.gov: NCT01596322). Setting: Mbarara, Uganda. Participants: Adult PLHIV enrolled at the start of antiretroviral therapy (ART) and observed every 3 to 4 months from 2005 to 2015. Measurements: The exposure of interest was time-varying efavirenz use, defined as use during the 7 days and in 60 or more of the 90 days before a study visit, compared with nevirapine use. Self-reported outcomes were depression, defined as a mean score greater than 1.75 on the Hopkins Symptom Checklist depression subscale, and suicidal ideation. Multivariable-adjusted generalized estimating equations (GEE) logistic regression, Cox proportional hazards regression, and marginal structural models were fit to estimate the association between efavirenz use and the risk for depression and suicidal ideation. Results: 694 participants (median age, 33 years; median pretreatment CD4+ count, 1.8 × 109 cells/L) contributed 1200 person-years of observation (460 person-years receiving efavirenz). No baseline differences in depression or suicidal ideation were found between patients ever exposed to efavirenz and those never exposed to efavirenz and receiving nevirapine (P > 0.80 for both). Of 305 participants ever-exposed to efavirenz, 61 (20.0%) and 19 (6.2%) had depression and suicidal ideation, respectively, on at least 1 follow-up visit, compared with 125 (32.1%) and 47 (12.1%) of the 389 who received nevirapine. In adjusted GEE models, efavirenz use was associated with decreased odds of depression compared with nevirapine use (adjusted odds ratio, 0.62 [95% CI, 0.40 to 0.96]) and was not significantly associated with suicidal ideation (adjusted odds ratio, 0.61 [CI, 0.30 to 1.25]). Time-to-event and marginal structural models yielded similar estimates. Limitation: Nonrandom assignment to treatment and substantial differences between the efavirenz and nevirapine groups. Conclusion: No evidence was found that use of efavirenz in first-line ART increased the risk for depression or suicidal ideation compared with nevirapine use among PLHIV in Uganda. Primary Funding Source: National Institutes of Health.


Asunto(s)
Fármacos Anti-VIH/efectos adversos , Benzoxazinas/efectos adversos , Depresión/inducido químicamente , Infecciones por VIH/tratamiento farmacológico , Nevirapina/efectos adversos , Ideación Suicida , Adulto , Alquinos , Fármacos Anti-VIH/uso terapéutico , Benzoxazinas/uso terapéutico , Ciclopropanos , Depresión/epidemiología , Femenino , Infecciones por VIH/psicología , Humanos , Masculino , Nevirapina/uso terapéutico , Estudios Prospectivos , Uganda/epidemiología
18.
J Clin Microbiol ; 56(1)2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29046412

RESUMEN

Microscopic diagnosis of malaria using Giemsa-stained blood smears is the standard of care in resource-limited settings. These smears represent a potential source of DNA for PCR testing to confirm Plasmodium infections or for epidemiological studies of archived samples. Therefore, we assessed the use of DNA extracts from stained blood smears for the detection of Plasmodium species using real-time PCR. We extracted DNA from archived blood smears and corresponding red blood cell pellets collected from asymptomatic children in southwestern Uganda in 2010. We then performed real-time PCR followed by high-resolution melting (HRM) to identify Plasmodium species, and we compared our results to those of microscopy. We analyzed a total of 367 blood smears and corresponding red blood cell pellets, including 185 smears (50.4%) that were positive by microscopy. Compared to microscopy, PCR-HRM analysis of smear DNA had a sensitivity of 93.0% (95% confidence interval [CI], 88.2 to 96.2%) and a specificity of 96.7% (95% CI, 93.0 to 98.8%), and PCR-HRM analysis of pellet DNA had a sensitivity of 100.0% (95% CI, 98.0 to 100.0%) and a specificity of 94.0% (95% CI, 89.4 to 96.9%). Identification of positive PCR-HRM results to the species level revealed Plasmodium falciparum (92.0%), Plasmodium ovale (5.6%), and Plasmodium malariae (2.4%). PCR-HRM analysis of DNA extracts from Giemsa-stained thick blood smears or corresponding blood pellets had high sensitivity and specificity for malaria diagnosis, compared to microscopy. Therefore, blood smears can provide an adequate source of DNA for confirmation of Plasmodium species infections and can be used for retrospective genetic studies.


Asunto(s)
Malaria/sangre , Malaria/parasitología , Tipificación Molecular/métodos , Plasmodium/clasificación , Plasmodium/genética , ADN Protozoario/genética , Técnicas Genéticas , Malaria/diagnóstico , Técnicas de Amplificación de Ácido Nucleico , Plasmodium/aislamiento & purificación , ARN Ribosómico 18S/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Sensibilidad y Especificidad , Uganda
19.
J Viral Hepat ; 25(12): 1582-1587, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30047565

RESUMEN

Hepatitis B virus (HBV) infection is hyperendemic in Cameroon, and healthcare workers (HCWs) are at high risk of infection. We aimed to assess prevalence, risk factors and vaccine coverage of HBV infection among HCWs in Cameroon. We conducted a cross-sectional study in 16 hospitals across all regions of Cameroon. HCWs were tested for HBV using rapid diagnostic tests (RDT). We collected data on socio-demographics and HBV vaccination status. We estimated prevalence of HBV and used Poisson regression models with robust standard errors to model the prevalence ratios of HBV positivity between covariates. We enrolled 1824 of 1836 eligible HCWs (97.5%). The mean age was 34 (SD: 10) years, 65.3% (n = 1787) were women, and 11.4% (n = 1747) had three or more doses of the HBV vaccine. Overall, we found a HBV prevalence of 8.7% (95% CI: 5.2%-14.3%). Patient transporters had the highest crude prevalence (14.3%; 95%CI: 5.4%-32.9%), whereas medical doctors had the lowest (3.2%; 95%CI: 0.8%-12.1%). The Far North Region had the highest prevalence of HBV (24.0%; 95%CI: 18.3%-30.8%). HBV prevalence decreased with increasing doses of the HBV vaccine (10.3% for no doses vs 3.5% for three or more doses; P < 0.001). In conclusion, approximately 1 in 12 HCWs in Cameroon have evidence of HBV infection, yet fewer than 1 in 6 have been fully vaccinated. Our results illustrate the urgent need to scale up systematic HBV screening and targeted vaccination of HCWs in the region.


Asunto(s)
Personal de Salud , Vacunas contra Hepatitis B/administración & dosificación , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Cobertura de Vacunación/estadística & datos numéricos , Adulto , Camerún/epidemiología , Estudios Transversales , Femenino , Vacunas contra Hepatitis B/inmunología , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Encuestas y Cuestionarios , Adulto Joven
20.
Eur J Clin Microbiol Infect Dis ; 37(8): 1465-1473, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29740714

RESUMEN

The Xpert MTB/RIF assay is a major advance for diagnosis of tuberculosis (TB) in high-burden countries but is limited in children by their difficulty to produce sputum. We investigated TB in sputum and stool from children with the aim of improving paediatric TB diagnosis. A prospective cohort of children with presumptive TB, provided two sputum or induced sputum at enrolment in a regional referral hospital in Uganda. Stool was collected from those started on TB treatment. All specimen were tested for Xpert MTB/RIF, mycobacteria growth indicator tube (MGIT), Lowenstein Jensen cultures and microscopy (except stool). We compared TB detection between age categories and assessed the performance of Xpert MTB/RIF in sputum and stool. Of the 392 children enrolled, 357 (91.1%) produced at least one sputum sample. Sputum culture yield was 13/357 (3.6%): 3/109 (2.6%), 3/89 (3.2%), 3/101 (2.6%) and 4/44 (8.2%) among children of < 2, 2-5, ≥ 5-10 and > 10 years, respectively (p = 0.599). Xpert MTB/RIF yield was 14/350 (4.0%): 3/104 (2.9%), 4/92 (4.3%), 3/88 (2.9%) and 4/50 (.0%), respectively (p = 0.283). Sensitivity and specificity of Xpert MTB/RIF in sputum against sputum culture were 90.9% (95% CI 58.7-99.8) and 99.1% (99.1-99.8). In stool, it was 55.6% (21.2-86.3) and 98.2% (98.2-100) against Xpert MTB/RIF and culture in sputum. Only a minority of children had microbiologically confirmed TB with a higher proportion in children above 10 years. Although sensitivity of Xpert MTB/RIF in stool was low, with good optimization, it might be a good alternative to sputum in children.


Asunto(s)
Heces/microbiología , Infecciones por VIH/epidemiología , Esputo/microbiología , Tuberculosis/diagnóstico , Adolescente , Envejecimiento , Niño , Preescolar , Infecciones por VIH/complicaciones , Humanos , Lactante , Mycobacterium tuberculosis/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico , Prevalencia , Sensibilidad y Especificidad , Tuberculosis/complicaciones , Tuberculosis/epidemiología , Uganda/epidemiología
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