Research Articles

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Plasmodium falciparum genetic diversity and multiplicity of infection among asymptomatic and symptomatic malaria-infected individuals in Uganda
(Springer Nature, 2024-11-14) Mwesigwa, Alex; Ocan, Moses; Cummings, Bryan; Musinguzi, Benson; Kiyaga, Shahid; Kiwuwa, Steven M.; Okoboi, Stephen; Castelnuovo, Barbara; Bikaitwoha, Everd Maniple; Kalyango, Joan N.; Karamagi, Charles; Nankabirwa, Joaniter I.; Nsobya, Samuel L.; Byakika-Kibwika, Pauline
Background: Plasmodium falciparum (P. falciparum) remains a significant public health challenge globally, especially in sub-Saharan Africa (SSA), where it accounts for 99% of all malaria infections. The outcomes of P. falciparum infection vary, ranging from asymptomatic to severe, and are associated with factors such as host immunity, parasite genetic diversity, and multiplicity of infection (MOI). Using seven neutral microsatellite markers, the current study investigated P. falciparum genetic diversity and MOI in both asymptomatic and symptomatic malaria individuals in Uganda. Methods: This cross-sectional study analyzed 225 P. falciparum isolates from both asymptomatic and symptomatic malaria patients, ranging in age from 6 months to ≥ 18 years. P. falciparum genetic diversity, MOI, and multi-locus linkage disequilibrium (LD) were assessed through genotyping of seven neutral microsatellite markers: Poly-α, TA1, TA109, PfPK2, 2490, C2M34–313, and C3M69–383. Genetic data analysis was performed using appropriate genetic analysis software. Results: P. falciparum infections exhibited high genetic diversity in both asymptomatic and symptomatic individuals. The mean expected heterozygosity (He) ranged from 0.79 in symptomatic uncomplicated malaria cases to 0.81 in asymptomatic individuals. There was no significant difference (p = 0.33) in MOI between individuals with asymptomatic and symptomatic infections, with the mean MOI ranging from 1.92 in symptomatic complicated cases to 2.10 in asymptomatic individuals. Polyclonal infections were prevalent, varying from 58.5% in symptomatic complicated malaria to 63% in symptomatic uncomplicated malaria cases. A significant linkage disequilibrium (LD) was observed between asymptomatic and symptomatic uncomplicated/complicated infections (p < 0.01). Genetic differentiation was low, with FST values ranging from 0.0034 to 0.0105 among P. falciparum parasite populations in asymptomatic and symptomatic uncomplicated/complicated infections. Conclusion: There is a high level of P. falciparum genetic diversity and MOI among both symptomatic and asymptomatic individuals in Uganda. Asymptomatic carriers harbor a diverse range of parasites, which poses challenges for malaria control and necessitates targeted interventions to develop effective strategies.
The state of patient-centered care and associated factors at a large referral hospital in Northwestern Uganda: Perceptions of patients
(Elsevier, 2024-11-07) Aleni, Mary; Mwebesa, Edson; Twesigye, Deus; Andru, Monicah; Assusi, Mildred Edna; Atuhairwe, Irene; Nsubuga, Allan G.; Ewing, Helen; Roepke, Abbey
Background: A Patient-Centered Care (PCC) approach to health service delivery is considered one of the essential domains of healthcare quality. This has been shown to improve patient satisfaction with health services and patient outcomes, but it has not been fully embraced in many low and middle income countries. Purpose: To evaluate patients’ perceptions of PCC and identify the factors influencing perceived PCC at a large referral hospital in Northwestern Uganda. Materials and Methods: We conducted a descriptive cross-sectional correlational study. Four hundred and eighty (480) patients or their attendants participated in the study. Data was collected using an interviewer administered questionnaire. Statistical analysis was applied at univariate, bivariate and multivariate levels using Stata V.14 to assess the state of PCC, patient perceptions and factors associated with perceived PCC. Results: Sixty five percent (64.8 %) of the participants perceived they received PCC. Most of the dimensions of PCC were rated high on a 5-point Likert scale, with respect for patient’s values and preferences ranked highest; mean score of 3.9 (SD = 0.9) and coordination of care ranked lowest, mean score of 3.5 (SD = 0.9). Being outpatient, single or never in union had a reduced perception score of PCC. Patients who had heard of PCC had a higher perception of PCC. Conclusion: Patient-Centered Care was rated optimally at ARRH. All the PCC dimensions were rated highly except coordination of care and information, education and communication which could be improved by building the capacity of health workers in effective communication and coordination of health care services.
Adaptation and carry over effects of extreme sporadic heat stress in Culex mosquitoes
(Elsevier, 2024-10-09) Padde, John Roberts; Zhou, Yinghui; Chen, Yunxuan; Zhu, Yuxiao; Yang, Yuxuan; Hou, Min; Chen, Lu; Xu, Zhipeng; Zhang, Donghui; Chen, Lin
Mosquitoes, as temperature-sensitive ectothermic vectors, exhibit temperature-dependence. This study investigates Culex pipiens pallens (Cx. pallens) responses to abrupt temperature increases and their implications on mosquito physiology. First instar larvae (24hr post hatching) and newly enclosed adults (24hr post emergence) were separately exposed to heat shock regimes of 33 °C, 37 °C, and 42 °C for 3 days alongside a control temperature of 27 °C. Results showed that mortality was triggered at 42 °C within a day. Adult male mosquitoes were less tolerant to all temperatures than larvae and adult females (p < 0.05). Exposing larvae to constant temperatures for 3 days significantly decreased larvae's development time, growth rate and adult emergence (p < 0.05). Reproductive fitness was significantly reduced (p < 0.05) in males emerging from larvae exposed to 37 °C. Life table parameters showed significant increased mortality rate, kill power and decreased life expectancy at the embryonic stage (p < 0.05). Furthermore, heatwaves deactivated the Transient receptor protein ankyrin 1 at 37 °C (p < 0.05) in larvae but not adults. Calmodium, Heat shock protein 90, and small heat shock protein expression were significantly decreased in larvae at 37 °C (p < 0.05) as compared to larvae raised at 33 °C and 27 °C. In conclusion, we classified the heat waves into three categories: adaptable (33 °C), critical (37 °C), and fatal (42 °C). Prolonged exposure of Culex pallens larvae to extreme heat affects the male reproductive output. These findings may serve as an important reference for forecasting vector and pest dynamics and used to tailor mosquito prevention and control measures.
Novel anti-inflammatory peptide alleviates liver ischemia-reperfusion injury
(Journal of Biomedical Research, 2024-04-30) Xu, Xuejun; Sun, Kaineng; Chang, Hao; Shen, Chunxiang; Li, Xiangdong; Ni, Yangyue; Zhu, Yuxiao; Wang, Huiquan; Xiong, Ruiyan; Padde, Jon Rob; Xu, Zhipeng; Chen, Lin; Chen, Lu; Hou, Min; Pu, Liyong; Ji, Minjun
Ischemia-reperfusion injury (IRI) remains inevitable in liver surgeries, macrophages play a critical role in the development of IRI, but little is known about the macrophages regulate pathogenesis of IRI. Based on target guided screening, we identified a small 3 kDa peptide (SjDX5-271) from various schistosome egg-derived peptides that induced M2 macrophage polarization. SjDX5-271 treatment protected the mice against liver IRI through promoting M2 macrophage polarization, the protective effect was abrogated when the macrophages were depleted. Transcriptomic sequencing showed that the TLR signaling pathway was significantly inhibited in macrophages derived from the SjDX5-271 treatment group. We further identified that SjDX5-271 promotes M2 macrophage polarization by inhibiting the TLR4/MyD88/NF-κB signaling pathway and further alleviates hepatic inflammation in liver IRI. Collectively, SjDX5-271 exhibits promising therapeutic effects in IRI and represents a novel therapeutic approach for IRI, even in immune-related diseases. This study revealed the development of a new biologic from the parasite and enhanced our understanding of host-parasite interplay, providing a blueprint for future therapies for immune-related diseases.
Knowledge, attitudes and barriers of breast self-examination among women in Nyio Ward, Arua City
(University of Warwick, 2024-09-11) Nabirye, Halima
Breast self-examination (BSE) is an effective, inexpensive and simple screening technique for examiningbreasts monthly to detect breast cancer. Among women diagnosed with breast cancer in Uganda, 89 per centof them present with stage III or IV, which has a poor prognosis. This study was conducted to assessknowledge, attitudes and barriers regarding BSE among women in Nyio ward, Arua City, Uganda.A descriptive cross-sectional study was conducted among 354 women selected by cluster sampling andrandom walk method. Data was entered into Microsoft Excel, coded and analysed using the SPSS version 23.Knowledge of BSE among the participants was low. Less than half of the respondents (47.5 per cent) had everheard about BSE as means of early detection of breast cancer and only 23.2 per cent knew how to performBSE. The majority (95.8 per cent) had a positive attitude towards BSE practice, 85.7 per cent believed BSE iscrucial in detecting breast cancer early, and most (83.3 per cent) agreed early detection increases the chancesof long-term survival. The most common barrier towards BSE was lack of awareness.A multidisciplinary approach, including the use of mass media, is required to create awareness about BSEand to reach a broader community.
Pharmacognostical evaluation and description of the leaf and root bark of Citropsis articulata Swingle & Kellerman
(Elsevier, 2024-09-14) Amaza, Ronald Anyase; Amutuhaire, Treasure Angie; Tusiimire, Jonans; Amito, Vivian Sharon; Ajayi, Clement Olusoji; Angupale, Jimmy Ronald; Abdelgadir, Abdelgadir Alamin; Anywar, Godwin; Ogwang, Patrick Engeu
Background: Citropsis articulata Swingle & Kellerman (Family Rutaceae) is a renowned African traditional medicinal plant for the management of erectile dysfunction. The root bark is more commonly used than the leaves. Little has been done to evaluate the pharmacognostical parameters of both parts. Purpose: The aim of this study was to determine the pharmacognostical parameters of C. articulata leaves and root bark. Methods: The plant parts were collected, washed, dried, and extracted by decoction and soxhlation. The World Health Organisation quality control methods for herbal materials were generally followed for the pharmacognostical evaluation of the root bark and leaf. This involved macroscopic and microscopic analysis, physicochemical analysis, hemolytic activity, and phytochemical analysis. Results: Macroscopically, the distillate of the root bark showed a fluorescent blue colour under ultra violet light of wavelength 254 nm. Microscopic examination revealed the presence of cellulose, lignified, suberized and cuticular cell walls. Numerous aleurone grains were noted in the root bark. Phytochemical analysis showed the presence of reducing sugars, free amino acids, L-arginine, coumarin, glycosides, phenols, phytosterols, saponins, steroids, tannins, terpenoids, alkaloids and flavonoids. Thin layer and high performance liquid fingerprints were also developed. The C. articulata root bark decoction and Soxhlet extracts contained 12.35 ± 0.05, and 110.00 ± 0.03 while the leaf decoction and Soxhlet extracts contained 4.97 ± 0.03 and 39.65 ± 0.00 mg/g diosgenin equivalent saponins respectively. The L-arginine content for the dried root bark decoction and Soxhlet was 2681 ± 7.29, 1660 ± 2.99 µg/g, while that for the leaf decoction and Soxhlet extracts was 135.60 ± 8.28, and 130.20 ± 2.83 µg/g respectively. Conclusion: This study distinguished the root bark and leaf of Citropsis articulata and offered vital information for the quality control and standardization of the plant materials.
Missed diagnosis of gestational diabetes mellitus due to selective screening: Evidence from a cross-sectional study in the West Nile Sub-Region, Uganda
(Taylor & Francis, 2024-03-13) Abindu, Vincent; Hope, Derick; Aleni, Mary; Andru, Monicah; Mangwi, Richard Ayiasi; Afayo, Victor; Oyet, Caesar; Kiconco, Ritah
Purpose: To ascertain the prevalence and risk factors of gestational diabetes mellitus (GDM) in pregnant women receiving antenatal care (ANC) services within the West Nile subregion of Uganda. An analytical cross-sectional study was conducted on 233 pregnant women who are within 24–28 weeks of gestation and are receiving ANC services in selected hospitals. GDM was diagnosed according to the World Health Organization (WHO) criteria (2013). A questionnaire and anthropometric measurements were used to obtain relevant data. The chi-square test and logistic regression were used to determine the association between GDM and the study variables, including participants’ sociodemographic and medical characteristics. The prevalence of hyperglycemia first detected in pregnancy among the participants tested was 8%. Overall, 7.45% had GDM and 0.53% had diabetes mellitus in pregnancy. The fasting plasma glucose test alone was positive in 86.7% of the GDM cases. The factors that were significantly associated with GDM included age ≥25 years (p = 0.017, AOR = 3.51) and body mass index (BMI) ≥25 kg/m2 (p = 0.024, AOR = 2.67). Out of the participants diagnosed with GDM, 28.6% did not have a known risk factor. Of the pregnant women with GDM, 57% would have been missed if the selective screening in the national clinical guidelines had been followed. Urinary tract infection (UTI) and Candida were detected in 36.36% and 13.85% of the participants, respectively. Conclusion: The study provides new data on the prevalence of GDM in rural settings in the West Nile subregion of Uganda. Of the participants, 7.5% were diagnosed with GDM, of which 57% would have been missed based on the selective screening of the national clinical guidelines. The study findings support the universal screening of GDM in pregnant women.
Evaluating psychometric properties of three mentoring scales among nurses and midwives in hospital settings: A methodological study
(Wiley, 2023-10-11) Kakyo, Tracy Alexis; Xiao, Lily Dongxia; Chamberlain, Diane
Scales used to evaluate nurses’ perspectives of mentoring programmes are mainly designed in developed countries, making them unsuitable for nurses and midwives working in resource-poor developing countries. To explore the psychometric properties of the perceived cost of mentoring (PCM) scale, negative mentoring experiences (NME) scale and relational mentoring index (RMI) for adaptation in hospital settings in Uganda. A cross-sectional study design was used. In total, 303 hospital nurses/midwives in Ugandan participated in the study to evaluate the psychometric properties of the three mentoring scales. Revisions based on word choice were made in adapting the scales to the Ugandan context. The PCM showed three factors (risk to reputation, mentoring effort and nepotism) and had an intra-class correlation (ICC) of 0.609 (95% CI, 0.324–0.793) and Cronbach's alpha of 0.705. The NME scale had two factors (lack of mentor expertise and mismatch between the dyad) consistent with the original scale with an ICC of 0.568 (95% CI, 0.271–0.767) and Cronbach's alpha of 0.841. The RMI showed two factors (individual influence and relational quality) with an ICC of 0.664 (95% CI, 0.410–0.824) and Cronbach's alpha of 0.933.The initial psychometric assessment indicates satisfactory validity and reliability of the scales for implementation among nurses and midwives within Ugandan hospital contexts. Subsequent research is warranted to validate the factor structures of the scales on a different sample. In using mentoring programmes to develop the hospital workforce, nurse and midwifery policymakers need to use culturally adapted and validated PCM, NME, and RMI scales to evaluate the quality of these mentoring programmes to maximise the benefits while avoiding unintended consequences.
The role of motivation in the initiation and maintening mentoring relationships among nurses and midwives
(Wiley, 2024-04-29) Kakyo, Tracy Alexis; Xiao, Lily Dongxia; Chamberlain, Diane
Nursing and midwifery literature has established the benefits of mentoring and challenges that affect the effectiveness of formal mentoring programmes. No studies have explored hospital nurses’ and midwives’ motivations to mentor in the absence of the obligatory status and associated rewards of institutionalised mentoring. A qualitative descriptive study with 35 nurses and midwives working in three public hospitals in the western, northern and northwestern parts of Uganda. Data were collected using semistructured interviews. Reflexive thematic analysis was applied to interpret the data. We have adhered to COREQ reporting guidelines. The study revealed three salient themes that capture nursing and midwifery professionals' mentoring perspectives. Participants expressed confidence in their inherent mentoring capacities and were often motivated by a desire to reciprocate prior mentoring experiences. Their mentoring approaches varied between self-focused and other-focused motivations, with some overlap in perspectives on hierarchical versus relational mentoring. Across the board, there was a strong consensus on the need of mentoring for individual clinicians, healthcare institutions and the broader profession. The study highlights five opportunities that can be harnessed to design future mentoring programmes. The findings delineate a complex interplay between self-centred and altruistic mentoring motivations, aligning with hierarchical or mutually beneficial mentoring paradigms. Nurse managers should tailor mentoring programmes to align with these intrinsic motivations, affirm the enduring need for mentoring, and leverage existing institutional resources to create both acceptable and efficient mentoring frameworks.
Exploring the dark side of informal mentoring: Experiences of nurses and midwives working in hospital settings in Uganda
(Wiley, 2024-04-12) Kakyo, Tracy Alexis; Xiao, Lily Dongxia; Chamberlain, Diane
Mentoring literature explores the dark side of mentoring as factors such as gender and race and how they affect the overall mentoring experience. The sociocultural context of the nursing and midwifery professions presents unique characteristics warranting a qualitative exploration of negative mentoring experiences. We aimed to characterise the dark side of mentoring based on informal mentoring relationships occurring among nurses and midwives working in hospitals. Utilising semistructured interviews in a qualitative descriptive design and reflexive thematic analysis, we examined the perceptions of 35 nurses and midwives from three public hospitals located in the Western, Northern and North-western regions of Uganda. Findings emerged in four overarching themes mentoring process deficits, mentoring relational problems, organisational challenges in mentoring and implications of negative mentoring experiences. Our study findings underscore that, while mentoring is frequently beneficial, it can also be interspersed with negative experiences arising from relational dynamics, particular mentoring processes and the overarching hospital environment. Notably, nurses and midwives actively transformed these challenges into opportunities for growth and self-improvement, while introspectively examining their roles in contributing to these negative experiences. Such a proactive approach highlights their resilience and steadfast commitment to professional development, even in the face of adversity.
Distribution and antifungal susceptibility profile of oropharyngeal Candida species isolated from people living with HIV in the era of universal test and treat policy in Uganda
(Sage Publishing, 2024-04-30) Musinguzi, Benson; Turyamuhika, Laban; Mwesigwa, Alex; Nalumaga, Pauline Petra; Kabajulizi, Immaculate; Njovu, Israel Kiiza; Mwebesa, Edson; Luggya, Tonny; Ocheng, Francis; Kateete, David Patrick; Itabangi, Herbert; Mboowa, Gerald; Sande, Obondo James; Achan, Beatrice
Despite the increased frequency of oropharyngeal candidiasis among people living with human immunodeficiency virus (HIV), its management is no longer effective due to empirical treatment and emergence of antifungal resistance (AFR). This study sought to investigate the prevalence of oropharyngeal candidiasis and assess the antifungal susceptibility profile of oropharyngeal Candida species isolated from people living with human immunodeficiency virus. Additionally, we evaluated the correlation between oropharyngeal candidiasis and CD4 T cell as well as viral load counts. A descriptive cross-sectional study was carried out from April to October 2023 in which 384 people living with HIV underwent clinical examination for oral lesions. Oropharyngeal swabs were collected and cultured on Sabouraud Dextrose agar to isolate Candida species which were identified using the matrix assisted laser desorption ionization time of flight mass spectrometry. Additionally, the antifungal susceptibility profile of Candida isolates to six antifungal drugs was determined using VITEK® (Marcy-l’Étoile, France) compact system. Data on viral load were retrieved from records, and CD4 T cell count test was performed using Becton Dickinson Biosciences fluorescent antibody cell sorter presto. The prevalence of oropharyngeal candidiasis was 7.6%. Oropharyngeal candidiasis was significantly associated with low CD4 T cell count and high viral load. A total of 35 isolates were obtained out of which Candida albicans comprised of 20 (57.1%) while C. tropicalis and C. glabrata comprised 4 (11.4%) each. C. parapsilosis, C. dubliniensis and C. krusei accounted for 2 (5.7%) each. Additionally, 7 (20%) isolates were resistant to fluconazole, 1 (2.9%) to flucytocine and 0.2 (5.7%) isolates were intermediate to caspofungin. However, specific specie isolates like C. albicans showed 20% (4/20), C. glabrata 50% (2/4) and C. krusei 50% (1/2) resistance to fluconazole. Additionally, C. krusei showed 50% resistance to flucytosine. The prevalence of oropharyngeal candidiasis (OPC) among people living with HIV was low, and there was a significant association between OPC and CD4 T cell count as well as viral load. C. albicans was the most frequently isolated oropharyngeal Candida species. C. glabrata and C. krusei exhibited the highest AFR among the non-albicans Candida species. The highest resistance was demonstrated to fluconazole.
Sero-antigen prevalence of lymphatic filariasis and risk factors of podoconiosis in Busiriba sub-county, Kamwenge district, Southwestern Uganda, August–September 2018
(Springer Nature, 2024-05-17) Mwesigye, Vicent; Musinguzi, Benson; Okongo, Benson; Mucunguzi, William; Kakaire, Michael Nyende; Migisha, Richard
Given the neglected nature of filariasis, especially in Uganda where data are scarce, this cross-sectional study aimed to determine the sero-antigen prevalence of lymphatic filariasis and risk factors associated with non-lymphatic filariasis (podoconiosis) in Busiriba Sub-county, Kamwenge District, Uganda, during August–September 2018, to inform targeted elimination efforts. We enrolled 101 participants, among whom 35 (34.7%) had podoconiosis. The sero-antigen prevalence of lymphatic filariasis was 1.0%. Older age and walking barefoot were associated with increased podoconiosis risk. Specifically, individuals aged 25–49 years with had 7.38 times higher odds of podoconiosis (adjusted odds ratio [aOR] = 7.38, 95% CI: 1.36–40.13) compared to those under 25 years, while those aged ≥ 50 years had even higher odds (aOR = 8.49, 95%CI: 1.44–50.15). Additionally, individuals who reported walking barefoot had 14 times higher odds of podoconiosis (aOR = 14.08; 95% CI: 2.49–79.50).
Plasmodium falciparum genetic diversity and multiplicity of infection based on msp-1, msp-2, glurp and microsatellite genetic markers in sub-Saharan Africa: a systematic review and meta-analysis
(Springer Nature, 2024-04-08) Mwesigwa, Alex; Ocan, Moses; Musinguzi, Benson; Nante, Rachel Wangi; Nankabirwa, Joaniter I.; Kiwuwa, Steven M.; Kinengyere, Alison Annet; Castelnuovo, Barbara; Karamagi, Charles; Obuku, Ekwaro A.; Nsobya, Samuel L.; Mbulaiteye, Sam M.; Byakika-Kibwika, Pauline
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. 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. 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%)
The impact of environmental and host factors on wolbachia density and efficacy as a biological tool
(Decoding Infection and Transmission, 2023-11-15) Padde, John Roberts; Lu, Qingyu; Long, Yuang; Zhang, Donghui; Hou, Min; Chen, Lu; Xu, Zhipeng; Chen, Lin; Ji, Minjun
Wolbachia, a bacterium found naturally in some species of Aedes and Culex mosquitoes, has gained significant attention for it's potential in controlling mosquito-borne diseases and suppressing mosquito populations. However, Wolbachia-mediated pathogen blockage, Wolbachia dynamics in field populations and vertical transmission have been reported to be density-dependent. Several factors, including host genetics, diet, temperature, and co-infections can influence Wolbachia titers within its host. The interplay between these factors can have significant influence on the effectiveness of Wolbachia-mediated pathogen blockage and cytoplasmic incompatibility. However, there is a knowledge gap regarding the regulation of Wolbachia density within its host, which could affect its effectiveness as a biocontrol tool. Therefore, this review aims to understand the complex tripartite association between the environment, host, and endosymbiont, and how these relationships are crucial in harnessing the full potential of Wolbachia as a biological tool. Further, we highlight how host, pathogen, and environmental factors influence Wolbachia density and how their interplay can impact CI and WMPB. We further review the strategies adopted to maintain/control Wolbachia densities in field populations.
A target-based discovery from a parasitic helminth as a novel therapeutic approach for autoimmune diseases.
(eBioMedicine, 2023-08-12) Ni, Yangyue; Xiong, Ruiyan; Zhu, Yuxiao; Luan, Ning; Yu, Chuanxin; Yang, Kun; Wang, Huiquan; Xu, Xuejun; Yang, Yuxuan; Sun, Siyu; Shi, Liyun; Chen, Lin; Chen, Lu; Hou, Min; Xu, Zhipeng; Lai, Ren; Jia, Minjun
Background: Regulatory T cells (Tregs) can alleviate the development of autoimmune and inflammatory diseases, thereby proposing their role as a new therapeutic strategy. Parasitic helminths have co-evolved with hosts to generate immunological privilege and immune tolerance through inducing Tregs. Thus, constructing a “Tregs-induction”-based discovery pipeline from parasitic helminth is a promising strategy to control autoimmune and inflammatory diseases. Methods: The gel filtration chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC) were used to isolate immunomodulatory components from the egg extracts of Schistosoma japonicum. The extracted peptides were evaluated for their effects on Tregs suppressive functions using flow cytometry, ELISA and T cell suppression assay. Finally, we carried out colitis and psoriasis models to evaluate the function of Tregs induced by helminth-derived peptide in vivo. Findings: Here, based on target-driven discovery strategy, we successfully identified a small 3 kDa peptide (SjDX5-53) from egg extracts of schistosome, which promoted both human and murine Tregs production. SjDX5-53 presented immunosuppressive function by arresting dendritic cells (DCs) at an immature state and augmenting the proportion and suppressive capacity of Tregs. In mouse models, SjDX5-53 protected mice against autoimmune-related colitis and psoriasis through inducing Tregs and inhibiting inflammatory T-helper (Th) 1 and Th17 responses. Interpretation: SjDX5-53 exhibited the promising therapeutic effects in alleviating the phenotype of immune-related colitis and psoriasis. This study displayed a screening and validation pipeline of the inducer of Tregs from helminth eggs, highlighting the discovery of new biologics inspired by co-evolution of hosts and their parasites. Funding: This study was supported by the Natural Science Foundation of China (82272368) and Natural Science Foundation of Jiangsu Province (BK20211586).
Investigating metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections: protocol for a laboratory-based cross-sectional study
(JMIR Publications, 2023-04-09) Njovu, Israel Kiiza; Nalumaga, Pauline Petra; Ampaire, Lucas; Nuwagira, Edwin; Mwesigye, James; Musinguzi, Benson; Kassaza, Kennedy; Taseera, Kabanda; Mukasa, James Kiguli; Bazira, Joel; Iramiot, Jacob Stanley; Baguma, Andrew; Bongomin, Felix; Kwizera, Richard; Achan, Beatrice; Cox, Michael J; King, Jason S; May, Robin; Ballou, Elizabeth R; Itabangi, Herbert
Background: Fungal-bacterial cocolonization and coinfections pose an emerging challenge among patients suspected of having pulmonary tuberculosis (PTB); however, the underlying pathogenic mechanisms and microbiome interactions are poorly understood. Understanding how environmental microbes, such as fungi and bacteria, coevolve and develop traits to evade host immune responses and resist treatment is critical to controlling opportunistic pulmonary fungal coinfections. In this project, we propose to study the coexistence of fungal and bacterial microbial communities during chronic pulmonary diseases, with a keen interest in underpinning fungal etiological evolution and the predominating interactions that may exist between fungi and bacteria. Objective: This is a protocol for a study aimed at investigating the metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections through determining and characterizing the burden, etiological profiles, microbial communities, and interactions established between fungi and bacteria as implicated among patients with presumptive PTB. Methods: This will be a laboratory-based cross-sectional study, with a sample size of 406 participants. From each participant, 2 sputa samples (one on-spot and one early morning) will be collected. These samples will then be analyzed for both fungal and bacterial etiology using conventional metabolic and molecular (intergenic transcribed spacer and 16S ribosomal DNA–based polymerase chain reaction) approaches. We will also attempt to design a genome-scale metabolic model for pulmonary microbial communities to analyze the composition of the entire microbiome (ie, fungi and bacteria) and investigate host-microbial interactions under different patient conditions. This analysis will be based on the interplays of genes (identified by metagenomics) and inferred from amplicon data and metabolites (identified by metabolomics) by analyzing the full data set and using specific computational tools. We will also collect baseline data, including demographic and clinical history, using a patient-reported questionnaire. Altogether, this approach will contribute to a diagnostic-based observational study. The primary outcome will be the overall fungal and bacterial diagnostic profile of the study participants. Other diagnostic factors associated with the etiological profile, such as incidence and prevalence, will also be analyzed using univariate and multivariate schemes. Odds ratios with 95% CIs will be presented with a statistical significance set at P<.05. Results: The study has been approved by the Mbarara University Research Ethic Committee (MUREC1/7-07/09/20) and the Uganda National Council of Science and Technology (HS1233ES). Following careful scrutiny, the protocol was designed to enable patient enrollment, which began in March 2022 at Mbarara University Teaching Hospital. Data collection is ongoing and is expected to be completed by August 2023, and manuscripts will be submitted for publication thereafter. Conclusions: Through this protocol, we will explore the metabolic and molecular ecological evolution of opportunistic pulmonary fungal coinfections among patients with presumptive PTB. Establishing key fungal-bacterial cross-kingdom synergistic relationships is crucial for instituting fungal bacterial coinfecting etiology.
“I don’t support It for my children”: perceptions of parents and guardians regarding the use of modern contraceptives by adolescents in Arua City, Uganda
(Hindawi, 2023-04-03) Vuamaiku, Godfrey Jalinga; Epuitai, Joshua; Andru, Monicah; Aleni, Mary
Despite the high rates of adolescent pregnancies, the utilization of modern contraceptives is still low among adolescents in Uganda which highlights a missed opportunity for the prevention of unwanted pregnancies among adolescents. We explored the perception of parents and guardians regarding the use of modern contraceptives by adolescents and the roles parents and guardians play in the use of modern contraceptives by the adolescents. A descriptive qualitative study was conducted in one of the suburbs of Arua city in the West Nile subregion in Uganda. Fifteen (15) in-depth interviews were conducted with parents and or guardians to explore their perceptions and roles regarding the use of modern contraceptives by adolescents. Thematic analysis was used in qualitative data analysis. Parents did not support adolescents’ use of modern contraceptives. Lack of parental support was related to perceptions that modern contraceptives promote sexual promiscuity, fear that it causes infertility and that it is incompatible with cultural, religious, and moral norms. Parents and guardians opted to emphasize the importance of abstinence, conformity with cultural and religious norms, and the need to focus on completing school instead of encouraging the use of modern contraceptives. Few parents and guardians supported the use of modern contraceptives, specifically condoms, to prevent unwanted pregnancy by the adolescents and parents/guardians, sexually transmitted infections, and early school dropouts. Parents and guardians expressed feelings of inadequacy related to discussions on contraception use with their adolescent children and therefore avoided talking about it. Our study reveals a lack of parental support regarding the use of modern contraceptives among adolescents. Public health interventions which promote intergenerational, socioculturally, and religiously appropriate communication should be instituted in the communities in order to promote sustainable adoption of modern contraceptive use among adolescents.
Single Nucleotide Variants (SNVs) of Angiotensin-Converting Enzymes (ACE1 and ACE2):
(Sage Publishing, 2023-04-03) Atiku, Saad Mahjub; Kasozi, Dennis; Campbell, Katrina
Background. Although it is common knowledge that the coronavirus disease of 2019 (COVID-19) and other viral infections have an uneven impact globally, the reasons for this are still indistinct. The absence of equivalent capacities worldwide in screening, testing, and reporting of cases is one of the ideas put forward to explain this discrepancy. The molecular developments are noteworthy, particularly the role played by single nucleotide polymorphisms (SNPs) in ACEs (ACE1 and ACE2). The virus can enter the host cell thanks to the transmembrane protein ACE2, which is a homolog of ACE1. Objectives. With a focus on the I/D genotype of ACE1 and the rs2285666 SNV of ACE2, we elucidated the prevalence of SNPs in ACE1 and ACE2 in various geographic locations. We examined the relationship between these SNPs and the global patterns of COVID-19 prevalence. Methods. 66 of the 127 articles obtained using PubMed, Google Scholar, and Google directly conformed to the search terms; geographical distribution of viral infections, the prevalence of COVID-19, ACE1, ACE2, SNPs, and prevalence of the DD genotype, and rs2285666. Results. The DD genotype of ACE1 and the rs2285666 SNV of ACE2 are vital in their gene expression and contribute greatly to viral disease susceptibility, development, and severity. There was generally a high prevalence of the DD genotype in Europe and America, where COVID-19 had a more devastating effect than in Asia and Africa. The prevalence of the SNV rs2285666 varied in the following order: East Asia> South Asia >America>Europe >Africa. However, there were conflicting agreements in the association of rs2285666 with COVID-19 susceptibility and prevalence. Conclusion. The ACE1 DD genotype and COVID-19 prevalence have been positively linked in a number of studies. The ACE2 rs2285666 SNV, however, has yielded no definitive results. To determine the relationship between these SNVs and COVID-19 incidence, more research is required.
High prevalence of malaria in pregnancy among women attending antenatal care at a large referral hospital in northwestern Uganda:
(PLOS One, 2023-04-05) Mangusho, Caleb; Mwebesa, Edson; Izudi, Jonathan; Aleni, Mary; Dricile, Ratib; Mangwi, Richard Ayiasi; Legason, Ismail Draguma
Background Malaria in pregnancy contributes to substantial morbidity and mortality among women in Uganda. However, there is limited information on the prevalence and factors associated with malaria in pregnancy among women in Arua district, northwestern Uganda. We, therefore, assessed the prevalence and factors associated with malaria in pregnancy among women attending routine antenatal care (ANC) clinics at Arua regional referral hospital in north-western Uganda. Methods We conducted an analytic cross-sectional study between October and December 2021. We used a paper-based structured questionnaire to collect data on maternal socio-demographic and obstetric factors and malaria preventive measures. Malaria in pregnancy was defined as a positive rapid malarial antigen test during ANC visits. We performed a modified Poisson regression analysis with robust standard errors to determine factors independently associated with malaria in pregnancy, reported as adjusted prevalence ratios (aPR) and 95% confidence intervals (CI). Results We studied 238 pregnant women with a mean age of 25.32±5.79 years that attended the ANC clinic, all without symptomatic malaria. Of the participants, 173 (72.7%) were in their second or third trimester, 117 (49.2%) were first or second-time pregnant women, and 212 (89.1%) reported sleeping under insecticide-treated bednets (ITNs) every day. The prevalence of malaria in pregnancy was 26.1% (62/238) by rapid diagnostic testing (RDT), with the independently associated factors being daily use of insecticide-treated bednets (aPR 0.41, 95% CI 0.28, 0.62), first ANC visit after 12 weeks of gestation (aPR1.78, 95% CI 1.05, 3.03), and being in the second or third trimester (aPR 0.45, 95% CI 0.26, 0.76). Conclusion The prevalence of malaria in pregnancy among women attending ANC in this setting is high. We recommend the provision of insecticide-treated bednets to all pregnant women and early ANC attendance to enable access to malaria preventive therapy and related interventions.
Factors associated with continuity of care in hypertension and type 2 diabetes among forcibly displaced persons in the Bidibidi refugee settlement in Uganda: Protocol for a cross-sectional, mixed-methods study
(Elsevier, 2023-03-02) Gyawali, Bishal; Dricile, Ratib; Dræbel, Tania Aase; Kyaddondo, David; Nakanjako, Rita; Nanfuka, Esther; Bygbjerg, Christian; Meyrowitsch, Dan Wolf; Skovdal, Morten
Background: Non-communicable diseases in humanitarian settings are generally under-researched, particularly in Africa and have been called a neglected crisis. Little is known about factors affecting access to and (dis)continuity of care for chronic conditions, such as hypertension (HTN) and type 2 diabetes among forcibly displaced persons (FDPs) in Uganda. Aim:To investigate factors affecting access to and (dis)continuity of HTN and/or type 2 diabetes care among FDPs in the Bidibidi refugee settlement, Uganda. Methods: A sequential explanatory mixed-methods design incorporating methodological and investigator triangulation will be conducted. The study aims to employ a community-based participatory research approach to equitably engage community members, researchers, and other stakeholders in the research process, recognising and maximising their diverse contributions. In phase 1, the quantitative arm of the study, 960 FDPs with HTN and/or type 2 diabetes will be interviewed about their sociodemographic characteristics, health status, migration experiences, social capital, and awareness, treatment, and control of these diseases. Participants will be purposively recruited from phase 1 as well as village health teams, healthcare providers, and policymakers to participate in phase 2, the qualitative study, in order to gain more insight into how mobility and social factors affect (dis)continuity of care among FDPs with HTN and/or type 2 diabetes. Discussion: The findings from phase 1 and phase 2 of the study will be integrated through a triangulation process to provide a more holistic and comprehensive insight into the factors affecting access to and (dis)continuity for HTN and/or type 2 diabetes care among FDPs. Understanding these factors is expected to pave the way for conceptualizing health-enabling environments and strengthening health systems for FDPs with chronic conditions. It is anticipated that the study will generate baseline evidence that might be beneficial in developing and implementing HTN and diabetes care models for FDPs in the region.

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