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In Mozambique, targeted provider-initiated HIV testing and counselling (PITC) is recommended where universal PITC is not feasible, but its effectiveness depends on healthcare providers' training. This study aimed to evaluate the effect of a Ministry of Health training module in targeted PITC on the HIV positivity yield, and identify factors associated with a positive HIV test. We conducted a single-group pre-post study between November 2018 and November 2019 in the triage and emergency departments of four healthcare facilities in Manhiça District, a resource-constrained semi-rural area. It consisted of two two-month phases split by a one-week targeted PITC training module ("observation phases"). The HIV positivity yield of targeted PITC was estimated as the proportion of HIV-positive individuals among those recommended for HIV testing by the provider. Additionally, we extracted aggregated health information system data over the four months preceding and following the observation phases to compare yield in real-world conditions ("routine phases"). Logistic regression analysis from observation phase data was conducted to identify factors associated with a positive HIV test. Among the 7,102 participants in the pre- and post-training observation phases (58.5% and 41.5% respectively), 68% were women, and 96% were recruited at triage. In the routine phases with 33,261 individuals (45.8% pre, 54.2% post), 64% were women, and 84% were seen at triage. While HIV positivity yield between pre- and post-training observation phases was similar (10.9% (269/2470) and 11.1% (207/1865), respectively), we observed an increase in yield in the post-training routine phase for women in triage, rising from 4.8% (74/1553) to 7.3% (61/831) (Yield ratio = 1.54; 95%CI: 1.11-2.14). Age (25-49 years) (OR = 2.43; 95%CI: 1.37-4.33), working in industry/mining (OR = 4.94; 95%CI: 2.17-11.23), unawareness of partner's HIV status (OR = 2.50; 95%CI: 1.91-3.27), and visiting a healer (OR = 1.74; 95%CI: 1.03-2.93) were factors associated with a positive HIV test. Including these factors in the targeted PITC algorithm could have increased new HIV diagnoses by 2.6%. In conclusion, providing refresher training and adapting the current targeted PITC algorithm through further research can help reach undiagnosed PLHIV, treat all, and ultimately eliminate HIV, especially in resource-limited rural areas., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Saura-Lázaro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Tuberculosis remains one of the top ten causes of mortality globally. Children accounted for 12% of all TB cases and 18% of all TB deaths in 2022. Paediatric TB is difficult to diagnose with conventional laboratory tests, and chest radiographs remain crucial. However, in low-and middle-income countries with high TB burden, the capacity for radiological diagnosis of paediatric TB is rarely documented and data on the associated radiation exposure limited., Methods: A multicentre, mixed-methods study is proposed in three countries, Mozambique, South Africa and Spain. At the national level, official registry databases will be utilised to retrospectively compile an inventory of licensed imaging resources (mainly X-ray and Computed Tomography (CT) scan equipment) for the year 2021. At the selected health facility level, three descriptive cross-sectional standardised surveys will be conducted to assess radiology capacity, radiological imaging diagnostic use for paediatric TB diagnosis, and radiation protection optimization: a site survey, a clinician-targeted survey, and a radiology staff-targeted survey, respectively. At the patient level, potential dose optimisation will be assessed for children under 16 years of age who were diagnosed and treated for TB in selected sites in each country. For this component, a retrospective analysis of dosimetry will be performed on TB and radiology data routinely collected at the respective sites. National inventory data will be presented as the number of units per million people by modality, region and country. Descriptive analyses will be conducted on survey data, including the demographic, clinical and programmatic characteristics of children treated for TB who had imaging examinations (chest X-ray (CXR) and/or CT scan). Dose exposure analysis will be performed by children's age, gender and disease spectrum., Discussion: As far as we know, this is the first multicentre and multi-national study to compare radiological capacity, radiation protection optimization and practices between high and low TB burden settings in the context of childhood TB management. The planned comparative analyses will inform policy-makers of existing radiological capacity and deficiencies, allowing better resource prioritisation. It will inform clinicians and radiologists on best practices and means to optimise the use of radiological technology in paediatric TB management., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Munyangaju et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To assess the repeatability of flow signal voids (FSV) measurements of the choriocapillaris (CC) and choroid (CH) in central serous chorioretinopathy (CSCR) by Swept-Source optical coherence tomography angiography (SS-OCTA)., Methods: Cross-sectional study including 104 eyes of 52 patients with unilateral CSCR. Two consecutive macular 6x6 mm SS-OCTA scans (Plex Elite 9000; Zeiss, Dublin, CA) were obtained from the affected eyes with persistent subretinal fluid (SRF) (CSCR group) and the fellow unaffected eyes (control group). FSV area and the number of contours measurements were analyzed using three slabs: inner CC, outer CC and CH. The repeatability of the measurements was assessed with intraclass correlation coefficients (ICC) and coefficients of variation (CV)., Results: In the CSCR group, ICCs for the FSV area in the three slabs were all ≥0.859, observing higher values for the outer CC and the CH (0.959 and 0.964) than for the inner CC (0.859). Similar ICC values were obtained for the FSV area in control eyes, observing the highest values for the outer CC (0.949), followed by the CH (0.932) and inner CC (0.844). Regarding the FSV number of contours measurements, ICCs were higher for the outer CC and CH (0.949 and 0.932) than for inner CC (0.844). CV for the FSV area was 4.7%, 3.8% and 8.6% in the CSCR eyes and 4.8%, 3.9% and 9.3% in the control group for the inner CC, outer CC and CH respectively., Conclusion: SS-OCTA offers good repeatability to quantify macular FSV in CSCR eyes and fellow eyes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Fernández-Vigo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Logistic regression (LR) is the most common prediction model in medicine. In recent years, supervised machine learning (ML) methods have gained popularity. However, there are many concerns about ML utility for small sample sizes. In this study, we aim to compare the performance of 7 algorithms in the prediction of 1-year mortality and clinical progression to AIDS in a small cohort of infants living with HIV from South Africa and Mozambique. The data set (n = 100) was randomly split into 70% training and 30% validation set. Seven algorithms (LR, Random Forest (RF), Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Naïve Bayes (NB), Artificial Neural Network (ANN), and Elastic Net) were compared. The variables included as predictors were the same across the models including sociodemographic, virologic, immunologic, and maternal status features. For each of the models, a parameter tuning was performed to select the best-performing hyperparameters using 5 times repeated 10-fold cross-validation. A confusion-matrix was built to assess their accuracy, sensitivity, and specificity. RF ranked as the best algorithm in terms of accuracy (82,8%), sensitivity (78%), and AUC (0,73). Regarding specificity and sensitivity, RF showed better performance than the other algorithms in the external validation and the highest AUC. LR showed lower performance compared with RF, SVM, or KNN. The outcome of children living with perinatally acquired HIV can be predicted with considerable accuracy using ML algorithms. Better models would benefit less specialized staff in limited resources countries to improve prompt referral in case of high-risk clinical progression., Competing Interests: The authors have declared that no competing interests exist.

Objective: World Health Organization recommends promoting breastfeeding without restricting its duration among HIV-positive women on lifelong antiretroviral treatment (ART). There is little data on breastfeeding duration and mother to child transmission (MTCT) beyond 24 months. We compared the duration of breastfeeding in HIV-exposed and HIV-unexposed children and we identified factors associated with postpartum-MTCT in a semi-rural population of Mozambique., Methods: This cross-sectional assessment was conducted from October-2017 to April-2018. Mothers who had given birth within the previous 48-months in the Manhiça district were randomly selected to be surveyed and to receive an HIV-test along with their children. Postpartum MTCT was defined as children with an initial HIV positive result beyond 6 weeks of life who initiated breastfeeding if they had a first negative PCR result during the first 6 weeks of life or whose mother had an estimated date of infection after the child's birth. Cumulative incidence accounting for right-censoring was used to compare breastfeeding duration in HIV-exposed and unexposed children. Fine-Gray regression was used to assess factors associated with postpartum-MTCT., Results: Among the 5000 mother-child pairs selected, 69.7% (3486/5000) were located and enrolled. Among those, 27.7% (967/3486) children were HIV-exposed, 62.2% (2169/3486) were HIV-unexposed and for 10.0% (350/3486) HIV-exposure was unknown. Median duration of breastfeeding was 13.0 (95%CI:12.0-14.0) and 20.0 (95%CI:19.0-20.0) months among HIV-exposed and HIV-unexposed children, respectively (p<0.001). Of the 967 HIV-exposed children, 5.3% (51/967) were HIV-positive at the time of the survey. We estimated that 27.5% (14/51) of the MTCT occurred during pregnancy and delivery, 49.0% (2551) postpartum-MTCT and the period of MTCT remained unknown for 23.5% (12/51) of children. In multivariable analysis, mothers' ART initiation after the date of childbirth was associated (aSHR:9.39 [95%CI:1.75-50.31], p = 0.001), however breastfeeding duration was not associated with postpartum-MTCT (aSHR:0.99 [95%CI:0.96-1.03], p = 0.707)., Conclusion: The risk for postpartum MTCT was nearly tenfold higher in women newly diagnosed and/or initiating ART postpartum. This highlights the importance of sustained HIV screening and prompt ART initiation in postpartum women in Sub-Saharan African countries. Under conditions where HIV-exposed infants born to mothers on ART receive adequate PMTCT, extending breastfeeding duration may be recommended., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Manhiça District, in Southern Mozambique harbors high HIV prevalence and a long history of migration. To optimize HIV care, we sought to assess how caregiver's mobility impacts children living with HIV (CLHIV)´s continuation in HIV care and to explore the strategies used by caregivers to maintain their CLHIV on antiretroviral treatment (ART)., Methods: A clinic-based cross-sectional survey conducted at the Manhiça District Hospital between December-2017 and February-2018. We enrolled CLHIV with a self-identified migrant caregiver (moved outside of Manhiça District ≤12 months prior to survey) and non-migrant caregiver, matched by the child age and sex. Survey data were linked to CLHIV clinical records from the HIV care and treatment program., Results: Among the 975 CLHIV screened, 285 (29.2%) were excluded due to absence of an adult at the appointment. A total of 232 CLHIV-caregiver pairs were included. Of the 41 (35%) CLHIV migrating with their caregivers, 38 (92.6%) had access to ART at the destination because either the caregivers travelled with it 24 (63%) or it was sent by a family member 14 (36%). Among the 76 (65%) CLHIV who did not migrate with their caregivers, for the purpose of pharmacy visits, 39% were cared by their grandfather/grandmother, 28% by an aunt/uncle and 16% by an adult brother/sister. CLHIV of migrant caregivers had a non-statistically significant increase in the number of previous reported sickness episodes (OR = 1.38, 95%CI: 0.79-2.42; p = 0.257), ART interruptions (OR = 1.73; 95%CI: 0.82-3.63; p = 0.142) and lost-to-follow-up episodes (OR = 1.53; 95%CI: 0.80-2.94; p = 0.193)., Conclusions: Nearly one third of the children attend their HIV care appointments unaccompanied by an adult. The caregiver mobility was not found to significantly affect child's retention on ART. Migrant caregivers adopted strategies such as the transportation of ART to the mobility destination to avoid impact of mobility on the child's HIV care. However this may have implications on ART stability and effectiveness that should be investigated in rural areas., Competing Interests: The authors have declared that no competing interests exist.

Background: HIV-infected men have higher rates of delayed diagnosis, reduced antiretroviral treatment (ART) retention and mortality than women. We aimed to assess, by gender, the first two UNAIDS 90 targets in rural southern Mozambique., Methods: This analysis was embedded in a larger prospective cohort enrolling individuals with new HIV diagnosis between May 2014-June 2015 from clinic and home-based testing (HBT). We assessed gender differences between steps of the HIV-cascade. Adjusted HIV-community prevalence was estimated using multiple imputation (MI)., Results: Among 11,773 adults randomized in HBT (7084 female and 4689 male), the response rate before HIV testing was 48.7% among eligible men and 62.0% among women (p<0.001). MI did not significantly modify all-age HIV-prevalence for men but did decrease prevalence estimates in women from 36.4%to 33.0%. Estimated proportion of HIV-infected individuals aware of their status was 75.9% for men and 88.9% for women. In individuals <25 years, we observed up to 22.2% disparity in awareness of serostatus between genders. Among individuals eligible for ART, similar proportions of men and women initiated treatment (81.2% and 85.9%, respectively). Fourfold more men than womenwere in WHO stage III/IV AIDS at first clinical visit. Once on ART, men had a twofold higher 18-month loss to follow-up rate than women., Conclusion: The contribution of missing HIV-serostatus data differentially impacted indicators of HIV prevalence and of achievement of UNAIDS targets by age and gender and men were missing long before the second 90. Increased efforts to characterize missing men and their needs will and their needs will allow us to urgently address the barriers to men accessing care and ensure men are not left behind in the UNAIDS 90-90-90 targets achievement., Competing Interests: The authors have declared that no competing interests exist.

Background: The implementation of quality HIV control programs is crucial for the achievement of the UNAIDS 90-90-90 targets and to motivate people living with HIV (PLWHIV) to link and remain in HIV-care. The aim of this mixed method cross-sectional study was to estimate the linkage and long-term retention in care of PLWHIV and to identify factors potentially interfering along the HIV-care continuum in southern Mozambique., Methods: A home-based semi-structured interview was conducted in 2015 to explore barriers and facilitators to the HIV-care cascade among individuals that had been newly HIV-diagnosed in community testing campaigns in 2010 or 2012. Linkage and long-term retention were estimated retrospectively through client self-reports and clinical records. Cohen's Kappa coefficient was calculated to measure the agreement between participant self-reported and documented cascade outcomes., Results: Among the 112 interviewed participants, 24 (21.4%) did not disclose their HIV-positive serostatus to the interviewer. While 84 (75.0%) self-reported having enrolled in care, only 69 (61.6%) reported still being in-care 3-5 years after diagnosis of which 17.4% reported having disengaged and re-engaged. An important factor affecting optimal continuum in HIV-care was the impact of the fear-based authoritarian relationship between the health system and the patient that could act as both driver and barrier., Conclusion: Special attention should be given to quantify and understand repeated cycles of patient disengagement and re-engagement in HIV-care. Strategies to improve the relationship between the health system and patients are still needed in order to optimally engage PLWHIV for long-term periods., Competing Interests: The authors have declared that no competing interests exist.

Background: Tuberculosis (TB) remains an important public health concern, especially in poorly resourced settings. TB diagnosis is challenging, particularly for children, who are the most vulnerable to its' impacts. Lack of knowledge and awareness of the disease compromises prompt diagnosis and treatment compliance., Objective: To gain insights regarding caretakers' knowledge of the aetiology and prevention of paediatric TB in southern Mozambique, to describe their care-seeking behaviours and to assess the acceptability of diagnostic procedures., Methods: A total of 35 caretakers were interviewed, all of which had children with TB compatible symptoms. Eleven were caretakers of children diagnosed with TB at the health facility, 11 of children for whom TB was excluded as a diagnosis at the health facility and 13 of children with TB compatible symptoms identified in the community. The first two groups took part in a TB incidence study, while the third group did not. All underwent the same semi-structured interviews, the results of which were analysed and compared using content analysis., Results: Even when confronted with signs suggestive of TB, most caretakers never suspected it or misinterpreted the signs, even among caretakers with TB and TB contacts. There was limited knowledge of TB, except among those undergoing treatment. The transgression of social norms was often presented as an explanation for TB in parallel to medically sound causes. The use of traditional care for prevention is widespread, but it varied for treatment purposes. TB diagnostic procedures were considered painful but were unanimously tolerated., Conclusions and Significance: Misconceptions of paediatric TB, associated complex care-seeking itineraries and negative feelings of the diagnostic procedures may result in delays, low adherence and lost to follow-up, which needs to be addressed by adequately framed health promotion approaches.

Methamphetamine (METH) is a psychostimulant that exhibits significant abuse potential. Although METH addiction is a major health and societal concern, no drug is currently approved for its therapeutic management. METH activates the central dopaminergic "reward" circuitry, and with repeated use increases levels of the neuromodulatory peptide neurotensin in the nucleus accumbens and ventral tegmental area. Previous studies in rats suggest that neurotensin agonism decreases METH self-administration, but these studies did not examine the effect of neurotensin agonism on the pattern of self-administration or open field locomotion. In our studies, we established intravenous METH self-administration in male, DBA/2J mice (fixed ratio 3, 2 hr sessions) and examined the effect of pretreatment with the NTS1 receptor agonist PD149163 on METH self-administration behavior. Locomotion following PD149163 was also measured up to 2 hours after injection on a rotarod and in an open field. Pretreatment with PD149163 (0.05 and 0.10 mg/kg, s.c.) significantly decreased METH self-administration. The pattern of responding suggested that PD149163 decreased motivation to self-administer METH initially in the session with more normal intake in the second hour of access. Voluntary movement in the open-field was significantly decreased by both 0.05 and 0.10 mg/kg (s.c.) PD149163 from 10-120 minutes after injection, but rotarod performance suggested that PD149163 did not cause frank sedation. These results suggest that a systemically delivered NTS1 receptor agonist decreases METH self-administration in mice. The pattern of self-administration suggests that PD149163 may acutely decrease motivation to self-administer METH before the drug is experienced, but cannot rule out that depression of voluntary movement plays a role in the decreased self-administration.

[This corrects the article DOI: 10.1371/journal.pone.0169757.].

Introduction: Non-tuberculous mycobacteria (NTM) can cause disease which can be clinically and radiologically undistinguishable from tuberculosis (TB), posing a diagnostic and therapeutic challenge in high TB settings. We aim to describe the prevalence of NTM isolation and its clinical characteristics in children from rural Mozambique., Methods: This study was part of a community TB incidence study in children <3 years of age. Gastric aspirate and induced sputum sampling were performed in all presumptive TB cases and processed for smear testing using fluorochrome staining and LED Microscopy, liquid and solid culture, and molecular identification by GenoType® Mycobacterium CM/AS assays., Results: NTM were isolated in 26.3% (204/775) of children. The most prevalent NTM species was M. intracellulare (N = 128), followed by M. scrofulaceum (N = 35) and M. fortuitum (N = 9). Children with NTM were significantly less symptomatic and less likely to present with an abnormal chest radiograph than those with M. tuberculosis. NTM were present in 21.6% of follow-up samples and 25 children had the same species isolated from ≥2 separate samples. All were considered clinically insignificant and none received specific treatment. Children with NTM isolates had equal all cause mortality and likelihood of TB treatment as those with negative culture although they were less likely to have TB ruled out., Conclusions: NTM isolation is frequent in presumptive TB cases but was not clinically significant in this patient cohort. However, it can contribute to TB misdiagnosis. Further studies are needed to understand the epidemiology and the clinical significance of NTM in children., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Chest radiography remains a critical tool for diagnosing intrathoracic tuberculosis (TB) in young children who are unable to expectorate. We describe the radiological findings in children under 3 years of age investigated for TB in the district of Manhiça, southern Mozambique, an area with a high prevalence of TB and HIV., Methods: Digital antero-posterior and lateral projections were performed and reviewed by two independent readers, using a standardized template. Readers included a local pediatrician and a pediatric radiologist blinded to all clinical information. International consensus case definitions for intra-thoracic TB in children were applied., Results: A total of 766 children were evaluated of whom 43 (5.6%) had TB. The most frequent lesion found in TB cases was air space consolidation (65.1%), followed by suggestive hilar lymphadenopathy (17.1%) and pleural effusion (7.0%). Air space consolidation was significantly more common in TB cases than in non-TB cases (odds ratio 8.9; 95% CI: 1.6-50.5), as were hilar lymphadenopathy (OR 17.2; 95% CI: 5.7-52.1). The only case with miliary infiltrates and 3 with pleural effusions occurred in HIV-infected children., Conclusion: Frequent air space consolidation complicates radiological distinction between TB and bacterial pneumonia in young children, underscoring the need for epidemiological contextualization and consideration of all relevant signs and symptoms.