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Dopamine Transporter Deficiency Syndrome (DTDS): expanding the clinical phenotype and precision medicine approaches
(MDPI, 2023-06) Waddington, Simon N.; Ng, Joanne; Barral, Serena; Kurian, Manju A.
Infantile parkinsonism-dystonia due to dopamine transporter deficiency syndrome (DTDS) is an ultrarare childhood movement disorder caused by biallelic loss-of-function mutations in the SLC6A3 gene. Advances in genomic analysis have revealed an evolving spectrum of SLC6A3-related neurological and neuropsychiatric disorders. Since the initial clinical and genetic characterisation of DTDS in 2009, there have been thirty-one published cases with a variety of protein-truncating variants (nonsense variants, splice-site changes, and deletions) and missense changes. Amino acid substitutions result in mutant proteins with impaired dopamine transporter function due to reduced transporter activity, impaired dopamine binding, reduced cell-surface expression, and aberrant posttranslational protein modification with impaired glycosylation. In this review, we provide an overview of the expanding clinical phenotype of DTDS and the precision therapies in development, including pharmacochaperones and gene therapy.
Advancing HIV Drug Resistance Technologies and Strategies: insights from South Africa’s Experience and Future Directions for Resource-Limited Settings
(MDPI, 2023-06) Steegen, Kim; Hans, Lucia; van Zyl, Gert U.; Claassen, Mathilda; Khan, Aabida; Pillay, Melendhran; Govender, Subitha; Bester, Phillip A.; van Straaten, Johanna M.; Kana, Vibha; Cutler, Ewaldé; Kalimashe, Monalisa N.; Lebelo, Ramokone L.; Moloi, Mokopi B. H.
Monitoring of HIV drug resistance (HIVDR) remains critical for ensuring countries attain and sustain the global goals for ending HIV as a public health threat by 2030. On an individual patient level, drug resistance results assist in ensuring unnecessary treatment switches are avoided and subsequent regimens are tailored on a case-by-case basis, should resistance be detected. Although there is a disparity in access to HIVDR testing in high-income countries compared to low- and middle-income countries (LMICS), more LMICs have now included HIVDR testing for individual patient management in some groups of patients. In this review, we describe different strategies for surveillance as well as where HIVDR testing can be implemented for individual patient management. In addition, we briefly review available technologies for HIVDR testing in LMICs, including Sanger sequencing, next-generation sequencing, and some point-of-care options. Finally, we describe how South Africa has implemented HIVDR testing in the public sector.
Laboratory services in the context of prevention of mother‑to‑child transmission of HIV testing requirements in Copperbelt Province, Zambia: a qualitative inquiry
(BioMed Central, 2023-07) Mwanza, Jonathan; Doherty, Tanya; Lubeya, Mwansa Ketty; Gray, Glenda E.; Mutale, Wilbroad; Kawonga, Mary
Introduction: Reliable and timely laboratory results are crucial for monitoring the Prevention of the Mother-to-Child Transmission (PMTCT) cascade, particularly to enable early HIV diagnosis and early intervention. We sought to explore whether and how laboratory services have been prepared to absorb new testing requirements following PMTCT Testand-Treat policy changes in three districts of Zambia. Method: We employed in-depth interviews and thematic data analysis, informed by the health system dynamic framework. Twenty-Six health workers were purposively selected and a document review of laboratory services in the context of PMTCT was undertaken. All face-to-face interviews were conducted in three local government areas in the Copperbelt Province (one urban and two rural) between February 2019 and July 2020. We extracted notes and markings from the transcripts for coding. Different codes were sorted into potential themes and the data extracted were put within the identified themes. Trustworthiness was confirmed by keeping records of all data field notes, transcripts, and reflexive journals. Results: The findings revealed that the health system inputs (infrastructure and supplies, human resources, knowledge, and information and finance) and service delivery were unequal between the rural and urban sites, and this affected the ability of health facilities to apply the new testing requirements, especially, in the rural-based health facilities. The major barriers identified include gaps in the capacity of the existing laboratory system to perform crucial PMTCT clinical and surveillance functions in a coordinated manner and insufficient skilled human resources to absorb the increased testing demands. The centralized laboratory system for HIV testing of mothers and exposed neonates meant facilities had to send specimens to other facilities and districts which resulted in high turnaround time and hence delayed HIV diagnosis. Conclusion: New guidelines implemented without sufficient capacitation of health system laboratory capacity severely limited the effectiveness of PMTCT program implementation. This study documented the areas relating to health system inputs and laboratory service delivery where greater support to enable the absorption of the new testing requirements is needed.
Current evidence on improving influenza vaccine uptake in low- and middle-income countries: a scoping review of determinants and interventions
(Elsevier, 2025-03) Tsotetsi, Lerato; Msibi, Tshepiso; Mashamba, Mulalo; Dietrich, Janan; Alam, Prima
Influenza is a vaccine-preventable disease affecting three to five million individuals across the globe annually. Low- and middle-income countries (LMICs) bear substantial health and economic consequences of influenza- related mortality. Despite this disproportionate burden, influenza vaccinations are seldom used across LMICs. In this article, we reviewed current evidence on improving influenza vaccine uptake within LMICs by examining key determinants and interventions. We conducted a scoping review of peer-reviewed studies pertaining to influenza vaccine uptake in LMICs. We searched five electronic databases for articles published 2014–2024, using terms relating to influenza vaccines, interventions, and context. Twenty-four articles met the inclusion criteria with sample sizes ranging from 38 to 9420. The authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines and synthesized the included articles using thematic analysis. All studies included in this review were cross-sectional and primarily used quantitative surveys. Most of the included studies were conducted in Sub-Saharan Africa (South Africa, Kenya, Malawi, and Sierra Leone) and the Middle East and North Africa (Tunisia, Jordan, Lebanon, and Egypt). Articles predominantly targeted vulnerable populations including elderly, pregnant women, and young children as well as healthcare workers. Participants across the included studies reported high levels of willingness to receive the influenza vaccination but lower levels of uptake. Having positive perceptions and attitudes towards the efficacy and safety of the vaccine, greater belief in disease susceptibility, physician recommendations, and a history of being vaccinated were associated with greater willingness to receive the influenza vaccine. Six articles explored national campaigns or researcher- led interventions to improve influenza vaccine uptake with educational campaigns positively changing attitudes towards influenza vaccination and integration of year-round vaccination campaigns with routine services as an effective vaccine delivery method.
Trends in national and ethnic burden of ovarian cancer mortality in South Africa (1999–2018): a population based, age-period-cohort and join point regression analyses
(BioMed Central, 2025-03) Olorunfemi, Gbenga; Libhaber, Elena; Musenge, Eustasius; Ezechi, Oliver C.
Ovarian cancer is the most lethal and third leading cause of gynaecological cancers globally and in South Africa (SA). However, its current mortality trends have not been evaluated in most sub-Saharan African Countries including South Africa that is currently undergoing epidemiological and health transitions. We evaluate the trends in the ovarian cancer mortality rates in SA over 20 years (1999–2018). Methods: Crude (CMR) and age standardised mortality rates (ASMR) of ovarian cancer was calculated based on national mortality data of South Africa. The overall and ethnic trends of ovarian cancer mortality among women aged 15 years and older from 1999 to 2018 was assessed using the Join point regression model, while Age-period-cohort regression analysis was conducted to evaluate the underlying impact of age, period and cohort on ovarian cancer mortality. Results: In all, 12,721 ovarian cancer deaths were reported in South Africa from 1999 to 2018 and the mortality rates increased from 2.34 to 3.21 per 100,00 women at 1.8% per annum. In 2018, the overall mean age at ovarian cancer death in South Africa was 62.30±14.96 years while the mean age at death among Black women (58.07±15.56 years), was about 11 years earlier than among White women (69.48±11.71 years). In 2018, the White ethnic group (4.93 deaths per 100,000 women) had about doubled the ovarian cancer ASMR for the non-Whites (Indian/Asians, 2.92/100,000 women, mixed race, 2.49/100,000 women and Black women (2.36/ 100,000 women). All the ethnic groups had increased ASMR with Black women (Average annual percent change, [AAPC]: 4.7%, P-value<0.001) and Indian/Asian women (AAPC: 2.5%, P-value<0.001) having the highest rise. Cohort mortality risk ratio of ovarian cancer increased with successive birth cohort from 0.35 among 1924–1928 birth cohorts to 3.04 among 1999–2003 cohort and the period mortality risk increased by about 13% and 7.5% from 1999 to 2003 to 2004–2008 (RR: 0.87, 95% CI: 0.80–0.94), and from 2004 to 2008 to 2009–2013 (RR: 1.075, 95% CI:1.004–1.152) respectively. The longitudinal age analysis revealed that ovarian cancer increased with age, but there was an exponential increase from 55 years. Conclusions: Our study showed that there was increasing trends in ovarian cancer mortality among all the South African ethnic groups, driven partly by increasing cohort and period mortality risks. We therefore highlight the huge burden of ovarian cancer in SA and the need for targeted intervention. Public health interventions geared towards reducing ovarian cancer mortality should be instituted and ethnic disparity should be incorporated in the cancer control policy
‘We do not like talking about our problems’: socialization and idealized masculinity as drivers of help-seeking avoidance among college men in South Africa
(BioMed Central, 2025-03) Sikweyiya, Yandisa; Jewkes, Rachel; Machisa, Mercilene; Mahlangu, Pinky; Brooke-Sumner, Carrie; Gibbs, Andrew; Dartnall, Elizabeth; Pillay, Managa
Background: This article explores how identities and contexts influence help-seeking avoidance behaviour among college men. Methods: This exploratory qualitative study purposively selected 88 male students (aged 18–30) from some universities and Technical and Vocational Training colleges (TVETs) in South Africa. Data were collected through focus group discussions (FGDs). Eight FGDs were conducted, one in each selected university (n = 2) and TVETs (n = 6) in 2018–2019. Data were analyzed using a thematic analysis approach. Results: We found that college men’s early life experiences and socialisation strongly influenced their ability to express emotion and access services when in need of help. The data also revealed a masculinity that men aspired to and wanted to be seen as embracing or personifying while on campus. Most men ascribed to an ideal of masculinity that made it difficult for them to share their feelings (e.g., emotional pain, sadness; and bottle their emotions) and seek help from campus-based counselors or peers. The few men who reported using campus mental health support services appraised them as unsuitable and unhelpful for them, and indicated a preference for services that were more culturally relevant. Most men indicated a preference for male counselors, of which there were very few. Conclusions: These findings may be useful for the formulation of evidence-based context-specific and culturally sensitive approaches for increasing men’s access to mental health and psychological support services on South African college campuses.
Refusal of male partner responsibility and pregnancy support: prevalence, associated factors and health outcomes in a cross sectional study in Harare, Zimbabwe
(BioMed Central, 2025-03) Shamu, Simukai; Machisa, Mercilene Tanyaradzwa; Shamu, Patience
Background The phenomenon of fathers refusing responsibility during pregnancy has not received adequate attention in African studies. This paper assesses associated factors and pregnancy-related outcomes when fathers refuse to support partners’ pregnancies and undertake parental responsibilities. Methods A cross-sectional survey of 15–49-year-old postnatal (1–6 weeks) women was conducted at six urban health facilities in Harare. Participants were interviewed about their male partners’ refusal to support their pregnancies and parenting, bride price payments (indicating marriage commitment), partner violence and control, alcohol abuse and family planning decision-making. Pregnancy health outcome data including antenatal care attendance, low birth weight (LBW)(<2500 g) and postnatal depression were collected through interviews and clinic records. Multiple regression models were built to assess gender-related factors and health outcomes associated with male partners’ refusal of parenting responsibilities. Results Of the 2042 women interviewed, 6.4% reported partner refusal to support the pregnancy or parenting. Higher odds of partner refusal of fathering responsibility were associated with partners not paying bride price (aOR 9.31; 95% CI 1.16–74.59), violence perpetration during pregnancy (aOR 2.84; 1.28–6.23), highly controlling behaviours (aOR 4.96; 2.83–8.69), alcohol abuse (aOR 1.78; 1.05–3.02), unintended pregnancy (aOR 3.72; 1.84–7.53) and partner refusal to use contraceptives (aOR 3.64; 1.86–7.14). Women who used contraceptives (aOR 0.40; 0.23–0.71), made joint (aOR 0.30; 0.14–0.67) or individual (aOR 0.25; 0.07–0.94) pregnancy decisions were protected from partner refusal of parenting responsibility. Women’s depressive symptomatology (aOR2.64; 1.52–4.59), LBW (aOR5.30; 1.18–23.74) and partner discouragement of antenatal care attendance (aOR 3.86; 1.13–13.17) were pregnancy outcomes associated with partner refusal of parenting responsibility. Conclusions Male partners’ refusal to acknowledge parenting responsibility was associated with men’s abusiveness, absence of commitment to long-term relationship/marriage, gender unequal practices and negative maternal and child health outcomes. Parenting programmes must be instituted and prioritise transforming traditional gender norms to improve fathering responsibilities.
Social influences on Moroccan and Pakistani immigrant women’s access and use of cervical cancer screening in Catalonia, Spain: a social network analysis
(BioMed Central, 2025) Harling, Guy; Lurgain, Jone G.; Peremiquel-Trillas, Paula; Ouaarab-Essadek, Hakima; Mellouki, Khadija; Sarif, Andleed
Background: Participation in cervical cancer (CC) screening programs is lower among immigrants compared to native women in many Western countries, in substantial due to lower knowledge and culturally influenced attitudes regarding self-care and prevention. Education and information programs alone have limited impact on individuals’ attitudes and behaviours, but may be bolstered by social influence methods such as peer support. Methods: In this study, we combined self-reported quantitative structural social network data with qualitative narratives and graphs to describe the social context of 12 Moroccan and 10 Pakistani immigrant women living in Catalonia, Spain. We used a survey protocol and semi-structured interviews to explore how women’s contacts influence their CC screening behaviours. Results: We identified strong gender and ethnic homophily in these women’s social networks. Despite maintaining frequent remote contact with their family ties, their immigrant peers were more influential in providing health information and advice. Furthermore, the women’s husbands played two conflicting roles as health promoters and as a barrier to the use of health prevention services. Conclusion: Our findings highlight the need to incorporate tailored social influence approaches in the design of behaviour change interventions. In this case, the use of peer-based programs to increase CC screening uptake among these two immigrant communities.
Opportunistic bacterial pathogens in bioaerosols emitted at municipal wastewater treatment plants, South Africa
(Nature Research, 2025-03) Poopedi, Evida; Pierneef, Rian; Singh, Tanusha; Gomba, Annancietar
Aeration tanks at wastewater treatment plants (WWTPs) emit significant amounts of bioaerosols containing potentially hazardous infectious material. Occupational exposure to airborne pathogens can pose health risks to WWTP workers. Bioaerosol samples collected at aeration tanks of two typical municipal WWTPs that use different aeration modes were analysed to investigate the composition and diversity of airborne bacteria in wastewater environments, using the Illumina MiSeq platform. Thirty-six potential airborne bacterial pathogens were identified in the air samples, and these were dominated by Bacillus, Enterococcus, Clostridium, Streptococcus, Acinetobacter, Enterobacter, Pseudomonas, Bacteroides fragilis, Acinetobacter baumannii, and Escherichia/Shigella. Bioaerosols from mechanical aeration tanks (72%, 26/36) had a relatively higher richness and diversity of airborne bacterial pathogens than diffused aeration tanks (17%, 6/36). Furthermore, most of the identified airborne bacterial pathogens (78%, 28/36) were classified as Risk Group 2 according to the revised South African Regulation for Hazardous Biological Agents, 2022, and up to 70% of these were gram-negative bacteria. The presence of potentially pathogenic bacteria in the ambient air at WWTPs suggests an elevated risk of bioaerosol exposure for workers. Therefore, further research and site-specific risk assessments are recommended to guide the implementation of effective bioaerosol strategies to protect workers’ health, with special attention paid to WWTPs that use mechanical aerators.
Socio-demographic disparities in basic under-two immunization coverage: insights from the 2016 Malawi demographic and health survey
(BioMed Central, 2025-03) Akokuwebe, Monica Ewomazino; Baruwa, Ololade Julius; Adeleye, Oluwafemi John; Gbadebo, Babatunde Makinde
Background: Childhood immunization is a vital component of public health, preventing the spread of infectious diseases and reducing child mortality. This study examines variations in basic immunization coverage across districts and explores socio-demographic disparities in immunization coverage among children aged 12–23 months in Malawi. Methods: The study employed a cross-sectional design, utilizing data from the 2016 MDHS, a nationally representative survey. The analysis included 3,248 children aged 12–23 months. Socio-demographic variables, including the child’s sex, maternal age, marital status (currently married), education, place of residence, region, wealth status, and employment status, were analysed using multivariate logistic regression models and a choropleth map to assess variations in basic immunization coverage across all 28 districts in Malawi. Results: The results showed that only 77.1% of children aged 12–23 months received basic immunization. The findings also highlighted significant variations in immunization coverage across different socio-demographic groups and among the 28 districts of Malawi. The highest coverage rates, ranging from 84.9 to 90.7%, were observed in Mwanza and Chiradzulu districts, while the lowest rates, between 65.3% and 68.0%, were found in Ntchisi, Blantyre, and Machinga districts. Multivariable analysis further indicated that children whose mothers were from a high household wealth index (OR = 1.45, 95% CI = 1.15–1.82), residing in rural areas (OR = 1.55, 95% CI = 1.20–2.01), currently married (OR = 1.33, 95% CI = 1.10–1.61), and with secondary or higher education (OR = 1.57, 95% CI = 1.11–2.21) were more likely to receive basic immunization. Conclusion: The study highlights low coverage of basic immunization in some districts as well as socio-demographic disparities in under-two immunization coverage in Malawi, necessitating tailored interventions such as educational campaigns and region-specific strategies.

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