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Many questions remain about the prevalence and effects of SARS-CoV-2 infection in malaria-endemic African countries like Uganda, particularly in vulnerable groups such as pregnant women. We describe SARS-CoV-2 immunoglobulin (Ig)G and IgM antibody responses and clinical outcomes in mother-infant dyads enrolled in malaria chemoprevention trials in Uganda. From December 2020-February 2022, among 400 unvaccinated pregnant women enrolled at 12-20 weeks gestation and followed through delivery, 128 (32%) were seronegative for anti-SARS-CoV-2 IgG and IgM at enrollment and delivery, 80 (20%) were infected prior to or early in pregnancy, and 192 (48%) were infected or re-infected with SARS-CoV-2 during pregnancy. We observed preferential binding of plasma IgG to Wuhan-Hu-1-like antigens in individuals seroconverting up to early 2021, and to Delta variant antigens in a subset of individuals in mid-2021. Breadth of IgG binding to all variants improved over time, consistent with affinity maturation of the antibody response in the cohort. No women experienced severe respiratory illness during the study. SARS-CoV-2 infection in early pregnancy was associated with lower median length-for-age Z-score at age 3 months compared with no infection or late pregnancy infect (-1.54 versus -0.37 and -0.51, P = 0.009). These findings suggest that pregnant Ugandan women experienced high levels of SARS-CoV-2 infection without severe respiratory illness. Variant-specific serology testing demonstrated evidence of antibody affinity maturation at the population level. Early gestational SARS-CoV-2 infection was associated with transient shorter stature in early infancy. Further research should explore the significance of this finding and define targeted measures to prevent infection in pregnancy.

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Tororo District, Uganda experienced a dramatic decrease in malaria burden from 2015-19 during 5 years of indoor residual spraying (IRS) with carbamate (Bendiocarb) and then organophosphate (Actellic) insecticides. However, a marked resurgence occurred in 2020, which coincided with a change to a clothianidin-based IRS formulations (Fludora Fusion/SumiShield). To quantify the magnitude of the resurgence, investigate causes, and evaluate the impact of a shift back to IRS with Actellic in 2023, we assessed changes in malaria metrics in regions within and near Tororo District. Malaria surveillance data from Nagongera Health Center, Tororo District was included from 2011-2023. In addition, a cohort of 667 residents from 84 houses was followed from August 2020 through September 2023 from an area bordering Tororo and neighboring Busia District, where IRS has never been implemented. Cohort participants underwent passive surveillance for clinical malaria and active surveillance for parasitemia every 28 days. Mosquitoes were collected in cohort households every 2 weeks using CDC light traps. Female Anopheles were speciated and tested for sporozoites and phenotypic insecticide resistance. Temporal comparisons of malaria metrics were stratified by geographic regions. At Nagongera Health Center average monthly malaria cases varied from 419 prior to implementation of IRS; to 56 after 5 years of IRS with Bendiocarb and Actellic; to 1591 after the change in IRS to Fludora Fusion/SumiShield; to 155 after a change back to Actellic. Among cohort participants living away from the border in Tororo, malaria incidence increased over 8-fold (0.36 vs. 2.97 episodes per person year, p<0.0001) and parasite prevalence increased over 4-fold (17% vs. 70%, p<0.0001) from 2021 to 2022 when Fludora Fusion/SumiShield was used. Incidence decreased almost 5-fold (2.97 vs. 0.70, p<0.0001) and prevalence decreased by 39% (70% vs. 43%, p<0.0001) after shifting back to Actellic. There was a similar pattern among those living near the border in Tororo, with increased incidence between 2021 and 2022 (0.93 vs. 2.40, p<0.0001) followed by a decrease after the change to Actellic (2.40 vs. 1.33, p<0.001). Among residents of Busia, malaria incidence did not change significantly over the 3 years of observation. Malaria resurgence in Tororo was temporally correlated with the replacement of An. gambiae s.s. by An. funestus as the primary vector, with a marked decrease in the density of An. funestus following the shift back to IRS with Actellic. In Busia, An. gambiae s.s. remained the primary vector throughout the observation period. Sporozoite rates were approximately 50% higher among An. funestus compared to the other common malaria vectors. Insecticide resistance phenotyping of An. funestus revealed high tolerance to clothianidin, but full susceptibility to Actellic. A dramatic resurgence of malaria in Tororo was temporally associated with a change to clothianidin-based IRS formulations and emergence of An. funestus as the predominant vector. Malaria decreased after a shift back to IRS with Actellic. This study highlights the ability of malaria vectors to rapidly circumvent control efforts and the importance of high-quality surveillance systems to assess the impact of malaria control interventions and generate timely, actionable data.

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BACKGROUND: Scale up of proven malaria control interventions has not been sufficient to control malaria in Uganda, emphasizing the need to explore innovative new approaches. Improved housing is one such promising strategy. This paper describes housing characteristics and their association with malaria burden in a moderate to high transmission setting in Uganda. METHODS: Between October and November 2021, a household survey was conducted in 1500 randomly selected households in Jinja and Luuka districts. Information on demographics, housing characteristics, use of malaria prevention measures, and proxy indicators of wealth were collected for each household. A finger-prick blood sample was obtained for thick blood smears for malaria from all children aged 6 months to 14 years in the surveyed households. Febrile children had a malaria rapid diagnostics test (RDT) done; positive cases were managed according to national treatment guidelines. Haemoglobin was assessed in children aged < 5 years. Households were stratified as having modern houses (defined as having finished materials for roofs, walls, and floors and closed eaves) or traditional houses (those not meeting the definition of modern house). Associations between malaria burden and house type were estimated using mixed effects models and adjusted for age, wealth, and bed net use. RESULTS: Most (65.5%) of the households surveyed lived in traditional houses. Most of the houses had closed eaves (85.5%), however, the use of other protective features like window/vent screens and installed ceilings was limited (0.4% had screened windows, 2.8% had screened air vents, and 5.2% had ceiling). Overall, 3,443 children were included in the clinical survey, of which 31.4% had a positive smear. RDT test positivity rate was 56.6% among children with fever. Participants living in modern houses had a significantly lower parasite prevalence by microscopy (adjusted prevalence ratio [aPR = 0.80]; 95% confidence interval [CI] 0.71 - 0.90), RDT test positivity rate (aPR = 0.90, 95%CI 0.81 - 0.99), and anaemia (aPR = 0.80, 95%CI 0.65 - 0.97) compared to those in traditional houses. CONCLUSION: The study found that even after adjusting for wealth, higher quality housing had a moderate protective effect against malaria, on top of the protection already afforded by recently distributed nets.

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Vivienda , Malaria , Uganda/epidemiología , Vivienda/estadística & datos numéricos , Preescolar , Lactante , Humanos , Niño , Adolescente , Malaria/epidemiología , Malaria/prevención & control , Femenino , Masculino , Prevalencia , Composición Familiar

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Background: Understanding COVID-19's impact on children is vital for public health policy, yet age-specific data is scarce, especially in Uganda. This study examines SARS-CoV-2 seroprevalence and risk factors among Ugandan children at two timepoints, along with COVID-19-related knowledge and practices in households, including adult vaccination status. Methods: Baseline surveys were conducted in 12 communities from April to May 2021 (post-Alpha wave) and follow-up surveys in 32 communities from November 2021 to March 2022 (Omicron wave). Household questionnaires and blood samples were collected to test for malaria by microscopy and for SARS-CoV-2 using a Luminex assay. Seroprevalence was estimated at both the survey and community level. Mixed-effects logistic regression models assessed the association between individual and household factors and SARS-CoV-2 seropositivity in children, adjusting for household clustering. Results: More households reported disruptions in daily life at baseline compared to follow-up, though economic impacts lingered. By the follow-up survey, 52.7% of adults had received at least one COVID-19 vaccine dose. Overall seroprevalence in children was higher at follow-up compared to baseline (71.6% versus 19.2%, p < 0.001). Seroprevalence in children ranged across communities from 6-37% at baseline and 50-90% at follow-up. At baseline, children from the poorest households were more likely to be infected. Increasing age remained the only consistent risk factor for SARS-CoV-2 seroconversion at both timepoints. Conclusions: Results indicate that a larger number of children were infected by the Delta and Omicron waves of COVID-19 compared to the Alpha wave. This study is the largest seroprevalence survey in children in Uganda, providing evidence that most children were infected with SARS-CoV-2 before the vaccine was widely available to pediatric populations. Pediatric infections were vastly underreported by case counts, highlighting the importance of seroprevalence surveys in assessing disease burden when testing and reporting rates are limited and many cases are mild or asymptomatic.

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Newly arrived refugees offer insights into malaria epidemiology in their countries of origin. We evaluated asymptomatic refugee children within 7 days of arrival in Uganda from South Sudan and the Democratic Republic of Congo (DRC) in 2022 for parasitemia, parasite species, and Plasmodium falciparum drug resistance markers. Asymptomatic P. falciparum infections were common in both populations. Coinfection with P. malariae was more common in DRC refugees. Prevalences of markers of aminoquinoline resistance (PfCRT K76T, PfMDR1 N86Y) were much higher in South Sudan refugees, of antifolate resistance (PfDHFR C59R and I164L, PfDHPS A437G, K540E, and A581G) much higher in DRC refugees, and of artemisinin partial resistance (ART-R; PfK13 C469Y and A675V) moderate in both populations. Prevalences of most mutations differed from those seen in Ugandans attending health centers near the refugee centers. Refugee evaluations yielded insights into varied malaria epidemiology and identified markers of ART-R in 2 previously little-studied countries.

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Antimaláricos , Resistencia a Medicamentos , Malaria Falciparum , Plasmodium falciparum , Proteínas Protozoarias , Refugiados , Humanos , Uganda/epidemiología , Antimaláricos/uso terapéutico , Antimaláricos/farmacología , Resistencia a Medicamentos/genética , Prevalencia , Preescolar , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/genética , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Malaria Falciparum/tratamiento farmacológico , Femenino , Masculino , Niño , Proteínas Protozoarias/genética , Lactante , Proteínas de Transporte de Membrana/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Sudán/epidemiología , Biomarcadores/sangre , Artemisininas/uso terapéutico , Artemisininas/farmacología , Parasitemia/epidemiología , Parasitemia/tratamiento farmacológico , Plasmodium malariae/genética , Plasmodium malariae/efectos de los fármacos

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BACKGROUND: Disruptions in malaria control due to COVID-19 mitigation measures were predicted to increase malaria morbidity and mortality in Africa substantially. In Uganda, long-lasting insecticidal nets (LLINs) are distributed nationwide every 3-4 years, but the 2020-2021 campaign was altered because of COVID-19 restrictions so that the timing of delivery of new nets was different from the original plans made by the National Malaria Control Programme. METHODS: A transmission dynamics modelling exercise was conducted to explore how the altered delivery of LLINs in 2020-2021 impacted malaria burden in Uganda. Data were available on the planned LLIN distribution schedule for 2020-2021, and the actual delivery. The transmission model was used to simulate 100 health sub-districts, and parameterized to match understanding of local mosquito bionomics, net use estimates, and seasonal patterns based on data collected in 2017-2019 during a cluster-randomized trial (LLINEUP). Two scenarios were compared; simulated LLIN distributions matching the actual delivery schedule, and a comparable scenario simulating LLIN distributions as originally planned. Model parameters were otherwise matched between simulations. RESULTS: Approximately 70% of the study population received LLINs later than scheduled in 2020-2021, although some areas received LLINs earlier than planned. The model indicates that malaria incidence in 2020 was substantially higher in areas that received LLINs late. In some areas, early distribution of LLINs appeared less effective than the original distribution schedule, possibly due to attrition of LLINs prior to transmission peaks, and waning LLIN efficacy after distribution. On average, the model simulations predicted broadly similar overall mean malaria incidence in 2021 and 2022. After accounting for differences in cluster population size and LLIN distribution dates, no substantial increase in malaria burden was detected. CONCLUSIONS: The model results suggest that the disruptions in the 2020-2021 LLIN distribution campaign in Uganda did not substantially increase malaria burden in the study areas.

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COVID-19 , Mosquiteros Tratados con Insecticida , Malaria , Control de Mosquitos , Uganda/epidemiología , Malaria/prevención & control , Malaria/epidemiología , Mosquiteros Tratados con Insecticida/estadística & datos numéricos , Humanos , Control de Mosquitos/estadística & datos numéricos , Control de Mosquitos/métodos , COVID-19/prevención & control , COVID-19/epidemiología

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BACKGROUND: Well-built housing limits mosquito entry and can reduce malaria transmission. The association between community-level housing and malaria burden in Uganda was assessed using data from randomly selected households near 64 health facilities in 32 districts. METHODS: Houses were classified as 'improved' (synthetic walls and roofs, eaves closed or absent) or 'less-improved' (all other construction). Associations between housing and parasitaemia were made using mixed effects logistic regression (individual-level) and multivariable fractional response logistic regression (community-level), and between housing and malaria incidence using multivariable Poisson regression. RESULTS: Between November 2021 and March 2022, 4.893 children aged 2-10 years were enrolled from 3.518 houses; of these, 1.389 (39.5%) were classified as improved. Children living in improved houses had 58% lower odds (adjusted odds ratio = 0.42, 95% CI 0.33-0.53, p < 0.0001) of parasitaemia than children living in less-improved houses. Communities with > 67% of houses improved had a 63% lower parasite prevalence (adjusted prevalence ratio 0.37, 95% CI 0.19-0.70, p < 0.0021) and 60% lower malaria incidence (adjusted incidence rate ratio 0.40, 95% CI 0.36-0.44, p < 0.0001) compared to communities with < 39% of houses improved. CONCLUSIONS: Improved housing was strongly associated with lower malaria burden across a range of settings in Uganda and should be utilized for malaria control.

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Vivienda , Mosquiteros Tratados con Insecticida , Malaria , Control de Mosquitos , Uganda/epidemiología , Preescolar , Vivienda/estadística & datos numéricos , Niño , Humanos , Malaria/epidemiología , Malaria/prevención & control , Mosquiteros Tratados con Insecticida/estadística & datos numéricos , Femenino , Control de Mosquitos/estadística & datos numéricos , Masculino , Incidencia , Prevalencia , Parasitemia/epidemiología , Parasitemia/parasitología

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BACKGROUND: Dentists have a legal and ethical obligation to obtain informed consent from patients before carrying out treatment. In Uganda, the process of obtaining informed consent in dentistry is not well documented. The aim of the present study was to determine dentists' perspectives and practices regarding informed consent to fixed prosthodontic treatment (FPT) in Kampala Metropolitan, Uganda. METHODS: A quantitative cross-sectional study was conducted among 153 dentists from July to September 2023. Data were collected using a semi-structured self-administered questionnaire that included both closed- and open-ended questions. The questionnaire included items on participants' sociodemographic information, perspectives, and practices about informed consent for FPT. Perspectives were rated using ten items on a five-point Likert scale. The minimum possible total score was 10, and the maximum possible score was 50. Descriptive statistics and Poisson regression were used to summarize and analyze the quantitative data, and the significance level was set at p < 0.05. Open-ended items were analyzed using content analysis. RESULTS: The majority (83.9%) of the participants were general dentists with working experience ranging from 1 to 38 years and a median of 8 years. The majority were familiar with the concept of informed consent and had positive perspectives regarding its use for FPT. The mean score for perspectives was 39.27 (SD, 5.42). However, there were variations in the practices of the dentists. More than three-quarters (87.6%) reported that they always obtained the patient's informed consent before FPT. Less than a third (29.4%) obtained written consent for FPT. About half of the dentists provided information regarding the procedure, benefits, and risks of treatment during the consent process. Bivariate analysis showed that the use of written consent for FPT was significantly (p < 0.05) associated with having a work experience of more than 10 years and having had training involving informed consent after undergraduate studies. CONCLUSION: The present study provides baseline data regarding perspectives and practices regarding informed consent for FPT among dentists in Uganda. It is recommended that regular training courses be developed to highlight the importance of improved informed consent practices for patient protection and to instruct dentists about obtaining valid informed consent. There is a need for future research to streamline guidelines for the informed consent process in dental care in Uganda.

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Consentimiento Informado , Pautas de la Práctica en Odontología , Humanos , Uganda , Estudios Transversales , Consentimiento Informado/legislación & jurisprudencia , Masculino , Femenino , Adulto , Pautas de la Práctica en Odontología/estadística & datos numéricos , Encuestas y Cuestionarios , Odontólogos/psicología , Persona de Mediana Edad , Actitud del Personal de Salud , Dentadura Parcial Fija

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[This corrects the article DOI: 10.1371/journal.pone.0244457.].

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BACKGROUND: In sub-Saharan Africa (SSA), Plasmodium falciparum causes most of the malaria cases. Despite its crucial roles in disease severity and drug resistance, comprehensive data on Plasmodium falciparum genetic diversity and multiplicity of infection (MOI) are sparse in SSA. This study summarizes available information on genetic diversity and MOI, focusing on key markers (msp-1, msp-2, glurp, and microsatellites). The systematic review aimed to evaluate their influence on malaria transmission dynamics and offer insights for enhancing malaria control measures in SSA. METHODS: The review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Two reviewers conducted article screening, assessed the risk of bias (RoB), and performed data abstraction. Meta-analysis was performed using the random-effects model in STATA version 17. RESULTS: The review included 52 articles: 39 cross-sectional studies and 13 Randomized Controlled Trial (RCT)/cohort studies, involving 11,640 genotyped parasite isolates from 23 SSA countries. The overall pooled mean expected heterozygosity was 0.65 (95% CI: 0.51-0.78). Regionally, values varied: East (0.58), Central (0.84), Southern (0.74), and West Africa (0.69). Overall pooled allele frequencies of msp-1 alleles K1, MAD20, and RO33 were 61%, 44%, and 40%, respectively, while msp-2 I/C 3D7 and FC27 alleles were 61% and 55%. Central Africa reported higher frequencies (K1: 74%, MAD20: 51%, RO33: 48%) than East Africa (K1: 46%, MAD20: 42%, RO33: 31%). For msp-2, East Africa had 60% and 55% for I/C 3D7 and FC27 alleles, while West Africa had 62% and 50%, respectively. The pooled allele frequency for glurp was 66%. The overall pooled mean MOI was 2.09 (95% CI: 1.88-2.30), with regional variations: East (2.05), Central (2.37), Southern (2.16), and West Africa (1.96). The overall prevalence of polyclonal Plasmodium falciparum infections was 63% (95% CI: 56-70), with regional prevalences as follows: East (62%), West (61%), Central (65%), and South Africa (71%). CONCLUSION: The study shows substantial regional variation in Plasmodium falciparum parasite genetic diversity and MOI in SSA. These findings suggest a need for malaria control strategies and surveillance efforts considering regional-specific factors underlying Plasmodium falciparum infection.

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Antígenos de Protozoos , Variación Genética , Malaria Falciparum , Proteína 1 de Superficie de Merozoito , Repeticiones de Microsatélite , Plasmodium falciparum , Proteínas Protozoarias , Plasmodium falciparum/genética , África del Sur del Sahara/epidemiología , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Proteínas Protozoarias/genética , Repeticiones de Microsatélite/genética , Antígenos de Protozoos/genética , Humanos , Proteína 1 de Superficie de Merozoito/genética , Marcadores Genéticos

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Background: Tororo District, Uganda experienced a dramatic decrease in malaria burden from 2015-19 following 5 years of indoor residual spraying (IRS) with carbamate (Bendiocarb) and then organophosphate (Actellic) insecticides. However, a marked resurgence occurred in 2020, which coincided with a change to a clothianidin-based IRS formulations (Fludora Fusion/SumiShield). To quantify the magnitude of the resurgence, investigate causes, and evaluate the impact of a shift back to IRS with Actellic in 2023, we assessed changes in malaria metrics in regions within and near Tororo District. Methods: Malaria surveillance data from Nagongera Health Center, Tororo District was included from 2011-2023. In addition, a cohort of 667 residents from 84 houses was followed from August 2020 through September 2023 from an area bordering Tororo and neighboring Busia District, where IRS has never been implemented. Cohort participants underwent passive surveillance for clinical malaria and active surveillance for parasitemia every 28 days. Mosquitoes were collected in cohort households every 2 weeks using CDC light traps. Female Anopheles were speciated and tested for sporozoites and phenotypic insecticide resistance. Temporal comparisons of malaria metrics were stratified by geographic regions. Findings: At Nagongera Health Center average monthly malaria cases varied from 419 prior to implementation of IRS; to 56 after 5 years of IRS with Bendiocarb and Actellic; to 1591 after the change in IRS to Fludora Fusion/SumiShield; to 155 after a change back to Actellic. Among cohort participants living away from the border in Tororo, malaria incidence increased over 8-fold (0.36 vs. 2.97 episodes per person year, p<0.0001) and parasite prevalence increased over 4-fold (17% vs. 70%, p<0.0001) from 2021 to 2022 when Fludora Fusion/SumiShield was used. Incidence decreased almost 5-fold (2.97 vs. 0.70, p<0.0001) and prevalence decreased by 39% (70% vs. 43%, p<0.0001) after shifting back to Actellic. There was a similar pattern among those living near the border in Tororo, with increased incidence between 2021 and 2022 (0.93 vs. 2.40, p<0.0001) followed by a decrease after the change to Actellic (2.40 vs. 1.33, p<0.001). Among residents of Busia, malaria incidence did not change significantly over the 3 years of observation. Malaria resurgence in Tororo was temporally correlated with the replacement of An. gambiae s.s. by An. funestus as the primary vector, with a marked decrease in the density of An. funestus following the shift back to IRS with Actellic. In Busia, An. gambiae s.s. remained the primary vector throughout the observation period. Sporozoite rates were approximately 50% higher among An. funestus compared to the other common malaria vectors. Insecticide resistance phenotyping of An. funestus revealed high tolerance to clothianidin, but full susceptibility to Actellic. Conclusions: A dramatic resurgence of malaria in Tororo was temporally associated with a change to clothianidin-based IRS formulations and emergence of An. funestus as the predominant vector. Malaria decreased after a shift back to IRS with Actellic. This study highlights the ability of malaria vectors to rapidly circumvent control efforts and the importance of high-quality surveillance systems to assess the impact of malaria control interventions and generate timely, actionable data.

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BACKGROUND: Provision of effective care to all women and newborns during the perinatal period is a viable strategy for achieving the Sustainable Development Goal 3 targets on reducing maternal and neonatal mortality. This study examined perinatal care (antenatal, intrapartum, postpartum) and its association with perinatal deaths at three district hospitals in Bunyoro region, Uganda. METHODS: A cross-sectional study was conducted in which a questionnaire was administered consecutively to 872 postpartum women before discharge who had attended antenatal care and given birth in the study hospitals. Data on care received during antenatal, labour, delivery, and postpartum period, and perinatal outcome were extracted from medical records of the enrolled postnatal women using a pre-tested structured tool. The care received from antenatal to 24 h postpartum period was assessed against the standard protocol of care established by World Health Organization (WHO). Poisson regression was used to assess the association between care received and perinatal death. RESULTS: The mean age of the women was 25 years (standard deviation [SD] 5.95). Few women had their blood tested for hemoglobin levels, HIV, and Syphilis (n = 53, 6.1%); had their urine tested for glucose and proteins (n = 27, 3.1%); undertook an ultrasound scan (n = 262, 30%); and had their maternal status assessed (n = 122, 14%) during antenatal care as well as had their uterus assessed for contraction and bleeding during postpartum care (n = 63, 7.2%). There were 19 perinatal deaths, giving a perinatal mortality rate of 22/1,000 births (95% Confidence interval [CI] 8.1-35.5). Of these 9 (47.4%) were stillbirths while the remaining 10 (52.6%) were early neonatal deaths. In the antenatal phase, only fetal examination was significantly associated with perinatal death (adjusted prevalence ratio [aPR] = 0.22, 95% CI 0.1-0.6). No significant association was found between perinatal deaths and care during labour, delivery, and the early postpartum period. CONCLUSION: Women did not receive all the required perinatal care during the perinatal period. Perinatal mortality rate in Bunyoro region remains high, although it's lower than the national average. The study shows a reduction in the proportion of perinatal deaths for pregnancies where the mother received fetal monitoring. Strategies focused on strengthened fetal status monitoring such as fetal movement counting methods and fetal heart rate monitoring devices during pregnancy need to be devised to reduce the incidence of perinatal deaths. Findings from the study provide valuable information that would support the strengthening of perinatal care services for improved perinatal outcomes.

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Muerte Perinatal , Niño , Recién Nacido , Femenino , Embarazo , Humanos , Adulto , Atención Perinatal , Uganda/epidemiología , Estudios Transversales , Hospitales de Distrito

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BACKGROUND: Understanding the burden of dyslipidemia and its associated factors among adult people living with HIV on dolutegravir (DTG) based anti-retroviral therapy (ART) is critical to provide clinical guidance and risk reduction strategies in our setting. METHODS: We conducted a cross-sectional study on adult people living with HIV on DTG based ART between July and August 2022 at Mengo Hospital, a private not for profit missionary hospital owned by the Church of Uganda. Dyslipidemia was defined as: Total cholesterol (TC) ≥ 5.2 mmol/l, or high-density lipoprotein (HDL) < 1 mmol/l for men and < 1.3 mmol/l for women, or triglycerides (TG) ≥ 1.7 mmol/l, and low-density lipoprotein (LDL) ≥ 3.4 mmol/l. A participant was considered to have dyslipidemia if they had any of the lipid profile parameters in the above ranges. Socio-demographic information, clinical data and behavioral characteristics were collected. Fasting lipid profile and fasting blood glucose levels were also measured. Bivariate and multivariate analyses were done using a generalized linear model regression of the Poisson family with a log link (modified Poisson) using robust standard errors since the prevalence of dyslipidemia was more than 10%. Adjusted prevalence ratios (PR) were reported with their 95% confidence intervals (CI). A p-value of less than 0.05 was considered statistically significant. RESULTS: A total of 341 participants were included. The prevalence of dyslipidemia was 78.0%, (95%CI:73.3-82.1). The highest prevalence was for low HDL (72.1%, 95%CI 67.1-76.7) followed by high TG (20.2%, 95%CI: 16.3-24.9), high TC (12.0%, 95%CI: 9.0-15.9) and high LDL (6.5%, 95%CI: 4.3-9.6). Female sex (aPR:1.55, 95%CI: 1.32-1.84, p < 0.001) and previous use of protease inhibitor (PI) based ART regimen (aPR:1.26, 95%CI: 1.04-1.53, p = 0.018) were significantly associated with dyslipidemia. CONCLUSION: We demonstrate that the prevalence of dyslipidemia is very high as it was present in more than three quarters of the study participants. Female sex and previous use of PI based ART regimen were significantly associated with dyslipidemia. Management of dyslipidemia should be integrated in the HIV treatment package and we recommend further inquiry into the temporal relationship between dyslipidemia and DTG among ART patients, if any.

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Dislipidemias , Adulto , Masculino , Humanos , Femenino , Centros de Atención Terciaria , Uganda/epidemiología , Estudios Transversales , Dislipidemias/epidemiología , Lipoproteínas LDL

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Early initiation of antiretroviral therapy (ART) after HIV diagnosis prevents HIV transmission, progression of HIV to AIDS and improves quality of life. However, little is known about the barriers to timely ART initiation among patients who test HIV positive in settings different from where they will receive HIV treatment, hence are referred in the routine setting. Therefore, we explored the perspectives of people living with HIV on barriers faced to initiate ART following HIV testing and referral for treatment. In this qualitative study, we purposively sampled and enrolled 17 patients attending the Mulago ISS clinic. We selected patients (≥18 years) who previously were received as referrals for HIV treatment and had delayed ART initiation, as ascertained from their records. We conducted in-depth interviews, which were audio recorded, transcribed and translated. We used Atlas.ti version 9 software for data management. Data analysis followed thematic and framework analysis techniques and we adopted the socio-ecological model to categorize final themes. Key themes were found at organizational level including; negative experiences at the place of HIV diagnosis attributed to inadequate counselling and support, unclear communication of HIV-positive results and ambiguous referral procedures; and, long waiting time when patients reached the HIV clinic. At individual level, the themes identified were; immediate denial with late acceptance of HIV-positive results attributed to severe emotional and psychological distress at receiving results, fear of perceived side effects and long duration on ART. At interpersonal level, we found that anticipated and enacted stigma after HIV diagnosis resulted in non-disclosure, discrimination and lack of social support. We found that challenges at entry (during HIV test) and navigation of the HIV care system in addition to individual and interpersonal factors contributed to delayed ART initiation. Interventions during HIV testing would facilitate early ART initiation among patients referred for HIV care.

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In modern medicine, vaccination is one of the most effective public health strategies to prevent infectious diseases. Indisputably, vaccines have saved millions of lives by reducing the burden of many serious infections such as polio, tuberculosis, measles, pneumonia, and tetanus. Despite the recent recommendation by the World Health Organization (WHO) to roll out RTS,S/AS01, this malaria vaccine still faces major challenges of variability in its efficacy partly due to high genetic variation in humans and malaria parasites. Immune responses to malaria vary between individuals and populations. Human genetic variation in immune system genes is the probable cause for this heterogeneity. In this review, we will focus on human genetic factors that determine variable responses to vaccination and how variation in immune system genes affect the immunogenicity and efficacy of the RTS,S/AS01 vaccine.

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Vacunas contra la Malaria , Malaria Falciparum , Malaria , Humanos , Lactante , África , Variación Genética

RESUMEN

BACKGROUND: Declines in malaria burden in Uganda have slowed. Modelling predicts that indoor residual spraying (IRS) and mass drug administration (MDA), when co-timed, have synergistic impact. This study investigated additional protective impact of population-based MDA on malaria prevalence, if any, when added to IRS, as compared with IRS alone and with standard of care (SOC). METHODS: The 32-month quasi-experimental controlled before-and-after trial enrolled an open cohort of residents (46,765 individuals, 1st enumeration and 52,133, 4th enumeration) of Katakwi District in northeastern Uganda. Consented participants were assigned to three arms based on residential subcounty at study start: MDA+IRS, IRS, SOC. IRS with pirimiphos methyl and MDA with dihydroartemisinin- piperaquine were delivered in 4 co-timed campaign-style rounds 8 months apart. The primary endpoint was population prevalence of malaria, estimated by 6 cross-sectional surveys, starting at baseline and preceding each subsequent round. RESULTS: Comparing malaria prevalence in MDA+IRS and IRS only arms over all 6 surveys (intention-to-treat analysis), roughly every 6 months post-interventions, a geostatistical model found a significant additional 15.5% (95% confidence interval (CI): [13.7%, 17.5%], Z = 9.6, p = 5e-20) decrease in the adjusted odds ratio (aOR) due to MDA for all ages, a 13.3% reduction in under 5's (95% CI: [10.5%, 16.8%], Z = 4.02, p = 5e-5), and a 10.1% reduction in children 5-15 (95% CI: [8.5%, 11.8%], Z = 4.7, p = 2e-5). All ages residents of the MDA + IRS arm enjoyed an overall 80.1% reduction (95% CI: [80.0%, 83.0%], p = 0.0001) in odds of qPCR confirmed malaria compared with SOC residents. Secondary difference-in-difference analyses comparing surveys at different timepoints to baseline showed aOR (MDA + IRS vs IRS) of qPCR positivity between 0.28 and 0.66 (p < 0.001). Of three serious adverse events, one (nonfatal) was considered related to study medications. Limitations include the initial non-random assignment of study arms, the single large cluster per arm, and the lack of an MDA-only arm, considered to violate equipoise. CONCLUSIONS: Despite being assessed at long time points 5-7 months post-round, MDA plus IRS provided significant additional protection from malaria infection over IRS alone. Randomized trials of MDA in large areas undergoing IRS recommended as well as cohort studies of impact on incidence. TRIAL REGISTRATION: This trial was retrospectively registered 11/07/2018 with the Pan African Clinical Trials Registry (PACTR201807166695568).

Asunto(s)

Insecticidas , Malaria , Niño , Humanos , Adolescente , Administración Masiva de Medicamentos , Uganda/epidemiología , Prevalencia , Estudios Transversales , Malaria/epidemiología , Malaria/prevención & control , Control de Mosquitos

RESUMEN

BACKGROUND: The in-utero transfer of malaria specific IgG to the fetus in Plasmodium falciparum infected pregnant women potentially plays a role in provision of immune protection against malaria in the first birth year. However, the effect of Intermittent Prophylactic Treatment in Pregnancy (IPTp) and placental malaria on the extent of in-utero antibody transfer in malaria endemic regions like Uganda remain unknown. The aim of this study was thus to establish the effect of IPTp on in-utero transfer of malaria specific IgG to the fetus and the associated immune protection against malaria in the first birth year of children born to mothers who had P. falciparum infection during pregnancy in Uganda. METHODS: We screened a total of 637 cord blood samples from a double blinded randomized clinical trial on Sulfadoxine-Pyrimethamine (SP) and Dihydroartemisinin-Piperaquine (DP) IPTp in a Ugandan birth cohort; study conducted from Busia, Eastern Uganda. Luminex assay was used to measure the cord levels of IgG sub-types (IgG1, IgG2, IgG3 and IgG4) against 15 different P. falciparum specific antigens, with tetanus toxoid (t.t) as a control antigen. Man-Whitney U test (non-parametric) in STATA (ver15) was used in statistical analysis of the samples. In addition, Multivariate cox regression analysis was used to determine the effect of maternal transfer of IgG on the incidence of malaria in the first birth year of children under study. RESULTS: Mothers on SP expressed higher levels of cord IgG4 against erythrocyte binding antigens (EBA140, EBA175 and EBA181) (p<0.05). Placental malaria did not affect cord levels of IgG sub-types against selected P. falciparum specific antigens (p>0.05). Children who expressed higher levels (75th percentile) of total IgG against the six key P. falciparum antigens (Pf SEA, Rh4.2, AMA1, GLURP, Etramp5Ag1 and EBA 175) had higher risk of malaria in the first birth year; AHRs: 1.092, 95% CI: 1.02-1.17 (Rh4.2); 1.32, 95% CI: 1.00-1.74 (PfSEA); 1.21, 95%CI: 0.97-1.52 (Etramp5Ag1); 1.25, 95%CI: 0.98-1.60 (AMA1); 1.83, 95%CI: 1.15-2.93 (GLURP) (GLURP), and 1.35,; 95%CI: 1.03-1.78 (EBA175). Children born to mothers categorized as poorest had the highest risk of malaria infections in the first birth year (AHR: 1.79, 95% CI: 1.31-2.4). Children born to mothers who had malaria infections during gestation had higher risk of getting malaria in the first birth year (AHR 1.30; 95%CI: 0.97-1.7). CONCLUSION: Malaria prophylaxis in pregnant mothers using either DP or SP does not affect expression of antibodies against P. falciparum specific antigens in the cord blood. Poverty and malaria infections during pregnancy are key risk factors of malaria infections in the first birth year of growth of children. Antibodies against P. falciparum specific antigens does not protect against parasitemia and malaria infections in the first birth year of children born in malaria endemic areas.

Asunto(s)

Antimaláricos , Malaria Falciparum , Malaria , Femenino , Humanos , Niño , Embarazo , Plasmodium falciparum , Antimaláricos/efectos adversos , Inmunoglobulina G , Uganda/epidemiología , Cohorte de Nacimiento , Placenta , Malaria Falciparum/epidemiología , Pirimetamina/efectos adversos , Combinación de Medicamentos

RESUMEN

Importance: Estimating the true burden of SARS-CoV-2 infection has been difficult in sub-Saharan Africa owing to asymptomatic infections and inadequate testing capacity. Antibody responses from serologic surveys can provide an estimate of SARS-CoV-2 exposure at the population level. Objective: To estimate SARS-CoV-2 seroprevalence, attack rates, and reinfection in eastern Uganda using serologic surveillance from 2020 to early 2022. Design, Setting, and Participants: This cohort study was conducted in the Tororo and Busia districts of eastern Uganda. Plasma samples from participants in the Program for Resistance, Immunology, Surveillance, and Modeling of Malaria in Uganda Border Cohort were obtained at 4 sampling intervals: October to November 2020, March to April 2021, August to September 2021, and February to March 2022. Each participant contributed up to 4 time points for SARS-CoV-2 serology, with almost half of all participants contributing at all 4 time points, and almost 90% contributing at 3 or 4 time points. Information on SARS-CoV-2 vaccination status was collected from participants, with the earliest reported vaccinations in the cohort occurring in May 2021. Main Outcomes and Measures: The main outcomes of this study were antibody responses to the SARS-CoV-2 spike protein as measured with a bead-based serologic assay. Individual-level outcomes were aggregated to population-level SARS-CoV-2 seroprevalence, attack rates, and boosting rates. Estimates were weighted by the local age distribution according to census data. Results: A total of 1483 samples from 441 participants living in 76 households were tested. Of the 441 participants, 245 (55.6%) were female, and their mean (SD) age was 16.04 (16.04) years. By the end of the Delta wave and before widespread vaccination, adjusted SARS-CoV-2 seroprevalence was 67.7% (95% credible interval [CrI], 62.5%-72.6%) in the study population. During the subsequent Omicron wave, 84.8% (95% CrI, 67.9%-93.7%) of unvaccinated, previously seronegative individuals were infected for the first time, and 50.8% (95% CrI, 40.6%-59.7%) of unvaccinated, already seropositive individuals were likely reinfected, leading to an overall seropositivity of 96.0% (95% CrI, 93.4%-97.9%) in this population. These results suggest a lower probability of reinfection in individuals with higher preexisting antibody levels. There was evidence of household clustering of SARS-CoV-2 seroconversion. No significant associations were found between SARS-CoV-2 seroconversion and gender, household size, or recent Plasmodium falciparum malaria exposure. Conclusions and Relevance: In this cohort study in a rural population in eastern Uganda, there was evidence of very high SARS-CoV-2 infection rates throughout the pandemic inconsistent with national level case data and high reinfection rates during the Omicron wave.

Asunto(s)

COVID-19 , SARS-CoV-2 , Humanos , Femenino , Adolescente , Masculino , Población Rural , COVID-19/epidemiología , Vacunas contra la COVID-19 , Estudios de Cohortes , Reinfección , Estudios Seroepidemiológicos , Uganda/epidemiología

RESUMEN

BACKGROUND: Uganda's current guidelines recommend immediate initiation of Anti-Retroviral Therapy (ART) for persons living with HIV in order to reduce HIV/AIDS related morbidity and mortality. However, not all eligible PLHIV initiate ART within the recommended time following HIV diagnosis. We assessed the prevalence and factors associated with delayed ART initiation among PLHIV referred for ART initiation, five years since rolling out the test and treat guidelines. METHODS: In this cross-sectional study, we enrolled adult patients referred to Mulago Immune Suppressive Syndrome (Mulago ISS) clinic for ART initiation from January 2017 to May 2021. We collected data on socio-demographics, HIV diagnosis and referral circumstances, and time to ART initiation using a questionnaire. The outcome of interest was proportion of patients that delayed ART, defined as spending more than 30 days from HIV diagnosis to ART initiation. We performed multivariable logistic regression and identified significant factors. RESULTS: A total of 312 patients were enrolled of which 62.2% were female. The median (inter-quartile range [IQR]) age and baseline CD4 count of the patients were 35 (28-42) years and 315 (118.8-580.5) cells/µL respectively. Forty-eight (15.4%) patients delayed ART initiation and had a median (IQR) time to ART of 92 (49.0-273.5) days. The factors associated with delayed ART initiation were; 1) having had the HIV diagnosis made from a private health facility versus public, (adjusted odds ratio [aOR] = 2.4 (95% confidence interval [CI] 1.1-5.5); 2) initial denial of positive HIV test results, aOR = 5.4 (95% CI: 2.0-15.0); and, 3) having not received a follow up phone call from the place of HIV diagnosis, aOR = 2.8 (95% CI: 1.2-6.8). CONCLUSION: There was significant delay of ART initiation among referred PLHIV within 5 years after the rollout of test and treat guidelines in Uganda. Health system challenges in the continuity of HIV care services negatively affects timely ART initiation among referred PLHIV in Uganda.

Asunto(s)

Síndrome de Inmunodeficiencia Adquirida , Fármacos Anti-VIH , Infecciones por VIH , Humanos , Adulto , Femenino , Masculino , Estudios Transversales , Uganda/epidemiología , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Terapia Antirretroviral Altamente Activa , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Recuento de Linfocito CD4 , Fármacos Anti-VIH/uso terapéutico

RESUMEN

Background: Subclinical anthracycline therapy related cardiac dysfunction (ATRCD) can be detected with speckle tracking echocardiographic image (STE), which is not widely available in Uganda. We aimed to investigate the role of the two conventional echocardiographic parameters [mitral annular plane systolic excursion (MAPSE) and mitral annular peak systolic tissue Doppler velocity (S')] on diagnosing subclinical ATRCD. Method and results: 207 cancer patients who underwent anthracycline based chemotherapy were recruited at baseline and followed up until 6 months after ending anthracycline therapy. Comprehensive echocardiographic data were collected at each visit. Global longitudinal strain (GLS) by STE was used as the gold standard diagnostic test to define the case of subclinical ATRCD. Data of the 200 patients who had no evidence of clinical ATRCD were analyzed. One hundred and seventy-two (86.0%) were female, with a median age of 42 years and 47 (23.5%) patients were diagnosed with subclinical ATRCD at the end of anthracycline therapy by GLS criteria. The area under the curve (AUC), cutoff point, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of reduction of MAPSE (ΔMAPSE) were 0.6736 (95% CI: 0.5885, 0.7587), ≥ 2 mm, 74.5% (95% CI: 59.7%, 86.1%), 54.9% (95% CI: 46.7%, 63.0%), 33.7% (95% CI: 24.7%, 43.6%), and 87.5% (95% CI: 79.2%, 93.4%). The AUC, cutoff point, sensitivity, specificity, PPV, and NPV of reduction of S' (ΔS') were 0.6018 (95% CI: 0.5084, 0.6953), ≥ 0.5 cm/s, 61.7% (95% CI: 46.4%, 75.5%), 52.7% (95% CI: 44.4%, 60.9%), 29.0% (95% CI: 20.4%, 38.9%), and 76.1% (95% CI: 72.4%, 88.6%). When ΔMAPSE and ΔS' are used as parallel test, the net sensitivity and specificity is 89.4% and 28.8%, respectively, the net PPV and NPV is 27.8% and 90.0%, respectively. Conclusion: The ΔMAPSE and ΔS' showed fairly good accuracy, sensitivity and NPV to detect subclinical ATRCD in Ugandan cancer patients. These conventional echocardiographic parameters may serve as screening tools for detecting subclinical ATRCD in resource limited settings.