Profile of HLA-B27-positive enthesitis/spondylitis-related arthritis in Senegal, West Africa.

BACKGROUND: Enthesitis/spondylitis-related arthritis (ERA) is a type of juvenile idiopathic arthritis (JIA) frequently associated with HLA-B27. In sub-Saharan Africa, HLA-B27-positive ERA hasn't been the subject of a specific study. OBJECTIVES: We aimed to describe the clinical features, disease activity, functional disability and treatment of HLA-B27-positive ERA at diagnosis in Senegal and compare the findings to other populations. METHODS: We conducted a retrospective study by reviewing the medical records of patients diagnosed with ERA with an age of symptom onset < 18 years according to the 2019 PRINTO provisional criteria for ERA from January 2012 to December 2022. We collected demographic, clinical, paraclinical and therapeutic data. Disease activity score was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Functional disability was assessed using Bath Ankylosing Spondylitis Functional Index (BASFI). RESULTS: A total of 31 patients with HLA-B27-positive ERA were included. Twenty of 31 (64.5%) were males. Twenty-seven (87%) were Fula (ethnicity). The median age at symptom onset and at diagnosis was 12 years and 19 years, respectively. Seven patients had a family history of Spondyloarthritis. Peripheral arthritis and enthesitis were the most common presenting features at disease onset. Peripheral arthritis was present in 29 (93.5%) and located in the lower limbs in 27/29 (93.1%) patients. Heel enthesitis was present in 26 (83.8%) patients. Axial involvement was present in 27 (87%) patients, dominated by low back pain and sacroiliac pain/ buttock pain in 24 (88.8%) and 22 (81.5%) patients, respectively. Seven (22.5%) patients had anterior uveitis. The ESR and CRP were elevated in 65.5% and 57.1% of cases, respectively. On imaging, sacroiliitis was found in 22 patients. The mean BASDAI was 5.5/10 (77.2% of patients had a high active disease; BASDAI ≥ 4/10). The mean ASDAS-ESR/CRP was 3.8. The mean BASFI was 5.4/10 (80% of patients had high functional disability; BASFI ≥ 4/10). Twenty-seven (87%) patients were treated with methotrexate and non-steroidal anti-inflammatory drugs. After 6 months of treatment, mean BASDAI was 3/10 and mean BASFI was 2.5/10. CONCLUSION: In our study, HLA-B27-positive ERA was found in our Senegalese cohort mainly in adolescents of the Fula ethnic group. 22 (70.9%) patients developed ankylosing spondylitis at adulthood. The disease was very active at the time of diagnosis with significant functional disability. Treatment was mainly based on methotrexate and NAISDs.

Does Growth Velocity Affect Associations between Birth Weight and Neurodevelopment for Infants Born Very Preterm?

OBJECTIVE: To determine how neonatal growth velocity affects the association between birth weight and neurodevelopmental outcomes in infants born preterm. STUDY DESIGN: This study is a secondary analysis of the Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants (MOBYDIck) randomized multicenter trial conducted in breastfed infants born at <29 weeks of gestation, whose mothers were supplemented with docosahexaenoic acid or placebo during the neonatal period. Neurodevelopmental outcomes were assessed at 18-22 months of corrected age using the Bayley-III cognitive and language composite scores. The role of neonatal growth velocity was assessed with causal mediation and linear regression models. Subgroup analyses were stratified by birth weight z-score categories (<25th, ≥25th-≤75th, and >75th percentiles). RESULTS: Neurodevelopmental outcomes were available for 379 children (mean gestational age, 26.7 ± 1.5 weeks). Growth velocity partially mediated the relationships between birth weight and cognitive (ß = -1.1; 95% CI, -2.2 to -0.02; P = .05) and language scores (ß = -2.1; 95% CI, -3.3 to -0.8; P = .002). An increase by 1 g/kg/day in growth velocity was associated with an increase by 1.1 point in the cognitive score (95% CI, -0.03 to 2.1; P = .06) and 1.9 point in the language score (95% CI, 0.7 to 3.1; P = .001), after adjustment for birth weight z-score. For children with birth weight <25th percentile, a 1 g/kg/day increase in growth velocity was associated with an increase by 3.3 points in the cognitive score (95% CI, 0.5 to 6.0; P = .02) and 4.1 points in the language score (95% CI, 1.3 to 7.0; P = .004). CONCLUSIONS: Postnatal growth velocity mediated the relationship between birth weight and neurodevelopmental performance, with larger effects for children with lower birth weight. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02371460.

Multiple Genes of Candida albicans Influencing Echinocandin Susceptibility in Caspofungin-Adapted Mutants.

Candida albicans is an opportunistic human fungal pathogen that causes invasive infections in immunocompromised individuals. Despite the high anticandidal activity among the echinocandins (ECNs), a first-line therapy, resistance remains an issue. Furthermore, many clinical isolates display decreased ECN susceptibility, a physiological state which is thought to lead to resistance. Determining the factors that can decrease susceptibility is of high importance. We searched for such factors genome-wide by comparing the transcriptional profiles of five mutants that acquired decreased caspofungin susceptibility in vitro in the absence of canonical FKS1 resistance mutations. The mutants were derived from two genetic backgrounds and arose due to independent mutational events, some with monosomic chromosome 5 (Ch5). We found that the mutants exhibit common transcriptional changes. In particular, all mutants upregulate five genes from Ch2 in concert. Knockout experiments show that all five genes positively influence caspofungin and anidulafungin susceptibility and play a role in regulating the cell wall mannan and glucan contents. The functions of three of these genes, orf19.1766, orf19.6867, and orf19.5833, were previously unknown, and our work expands the known functions of LEU42 and PR26. Importantly, orf19.1766 and LEU42 have no human orthologues. Our results provide important clues as to basic mechanisms of survival in the presence of ECNs while identifying new genes controlling ECN susceptibility and revealing new targets for the development of novel antifungal drugs.

Maternal High-Dose DHA Supplementation and Neurodevelopment at 18-22 Months of Preterm Children.

OBJECTIVES: To determine whether maternal supplementation with high-dose docosahexaenoic acid (DHA) in breastfed, very preterm neonates improves neurodevelopmental outcomes at 18 to 22 months' corrected age (CA). METHODS: Planned follow-up of a randomized, double-blind, placebo-controlled, multicenter trial to compare neurodevelopmental outcomes in breastfed, preterm neonates born before 29 weeks' gestational age (GA). Lactating mothers were randomized to receive either DHA-rich algae oil or a placebo within 72 hours of delivery until 36 weeks' postmenstrual age. Neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development third edition (Bayley-III) at 18 to 22 months' CA. Planned subgroup analyses were conducted for GA (<27 vs ≥27 weeks' gestation) and sex. RESULTS: Among the 528 children enrolled, 457 (86.6%) had outcomes available at 18 to 22 months' CA (DHA, N = 234, placebo, N = 223). The mean differences in Bayley-III between children in the DHA and placebo groups were -0.07 (95% confidence interval [CI] -3.23 to 3.10, P = .97) for cognitive score, 2.36 (95% CI -1.14 to 5.87, P = .19) for language score, and 1.10 (95% CI -2.01 to 4.20, P = .49) for motor score. The association between treatment and the Bayley-III language score was modified by GA at birth (interaction P = .07). Neonates born <27 weeks' gestation exposed to DHA performed better on the Bayley-III language score, compared with the placebo group (mean difference 5.06, 95% CI 0.08-10.03, P = .05). There was no interaction between treatment group and sex. CONCLUSIONS: Maternal DHA supplementation did not improve neurodevelopmental outcomes at 18 to 22 months' CA in breastfed, preterm neonates, but subgroup analyses suggested a potential benefit for language in preterm neonates born before 27 weeks' GA.

Use of SMOF lipid emulsion in very preterm infants does not affect the incidence of bronchopulmonary dysplasia-free survival.

BACKGROUND: We aim to assess whether the docosahexaenoic acid (DHA)-containing lipid emulsion (LE) SMOFlipid 20% (Fresenius Kabi Canada Ltd) is associated with bronchopulmonary dysplasia (BPD)-free survival at 36 weeks' postmenstrual age in very preterm infants. METHODS: This cohort study is nested in the MOBYDIck randomized clinical trial (NCT02371460), which investigated the effect of maternal DHA supplementation on BPD-free survival in breastfed very preterm infants born between 23 0/7 and 28 6/7 weeks' gestation in 16 Canadian neonatal intensive care units (2015-2018). Parenteral SMOF-LE was given to the infants according to the sites' routine care protocols. Relative risks (RRs) were estimated using a modified Poisson regression model with generalized estimating equations taking into account recruitment site, multiple birth, DHA supplementation, birth weight, sex, and gestational age. RESULTS: Among 528 infants (mean gestational age, 26.5 weeks [SD, 1.6]), 272 received SMOF-LE. Overall, 56.7% of the infants in the SMOF-LE group and 59.7% infants in the non-SMOF-LE group survived without BPD (adjusted RR, 0.94 [95% CI, 0.77-1.14]; P = 0.51). BPD rates were 39.3% in the SMOF-LE group vs 34.1% in the non-SMOF-LE group (adjusted RR, 1.10 [95% CI, 0.82-1.47]; P = 0.53). Severe BPD rates were 31.8% in the SMOF-LE group vs 28.8% in the non-SMOF-LE group (adjusted P = 0.59). Mortality was not significantly different between the SMOF-LE (6.7%) and non-SMOF-LE groups (9.5%; adjusted P = 0.40). CONCLUSION: In very preterm infants, intravenous DHA-containing SMOF-LE during the neonatal period was not associated with BPD-free survival.

Effect of Maternal Docosahexaenoic Acid Supplementation on Very Preterm Infant Growth: Secondary Outcome of a Randomized Clinical Trial.

INTRODUCTION: The aim of the study was to determine the effect of a maternal docosahexaenoic acid (DHA) supplementation during lactation, compared with a placebo, on the neonatal growth profile of breastfed very preterm infants. METHODS: Preterm infants' growth profile, growth velocity from birth to 36 weeks' postmenstrual age (PMA), and growth at 36 weeks' PMA were pre-specified secondary outcomes of a randomized placebo-controlled trial conducted in 16 Canadian neonatal intensive care units (2015-2018). Lactating mothers who delivered before 29 weeks' gestation were given 1.2 g of DHA daily or a placebo within 72 h of delivery and up to 36 weeks' PMA. Analyses were performed using a linear regression model with generalized estimating equations. RESULTS: 461 mothers and their 528 infants (DHA, N = 273; placebo, N = 255) were included with mean gestational age of 26.5 weeks (standard deviation [SD] = 1.6); 275 (52.1%) were males; mean birth weight was 895 g (SD = 240). DHA interaction with sex was significant on weight profile (interaction p < 0.001), weight velocity (interaction p = 0.05), and weight at 36 weeks' PMA (interaction p = 0.02). Females in the DHA group gained more weight compared to the placebo group (mean difference [MD], 52.6 g [95% confidence interval [CI]: 24.5-80.8], p < 0.001). Weight velocity was significantly higher in females of the DHA group (MD, 3.4 g/kg/day [95% CI: 0.6-6.2], p = 0.02). At 36 weeks' PMA, the weight of males in the DHA group was significantly smaller (MD, -88.9 g [95% CI: -166.2 to -11.6], p = 0.02). CONCLUSION: DHA positively affected female infants' neonatal weight profile and velocity and negatively affected male infants' weight at 36 weeks' PMA.

Antimicrobial susceptibility of select respiratory tract pathogens in Dakar, Senegal.

BACKGROUND: Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, and Streptococcus pneumoniae are the most common causative agents of respiratory tract infections (RTIs). The increase in resistance to current antibacterial agents highlights the need to monitor the resistance pattern of these bacterial pathogens. METHODOLOGY: In this study, we assessed the antibacterial susceptibility of these pathogens causing respiratory tract infections in Dakar, Senegal, during 2007-2008. A total of 290 bacterial isolates (75 H. influenzae, 10 M. catarrhalis, 105 S. pneumoniae, and 100 S. pyogenes) were collected. RESULTS AND CONCLUSIONS: All H. influenzae isolates were susceptible to amoxicillin/clavulanic acid, ofloxacin, clarithromycin, cephalosporins, and macrolides. Overall, 26.7% of H. influenzae isolates were completely resistant to ampicillin. Among the M. catarrhalis isolates, 30% were resistant to ampicillin. All the isolates of H. influenzae and M. catarrhalis that were resistant to ampicillin were beta-lactamase producing strains. Among the S. pneumoniae isolates, 33.3% isolates exhibited intermediate susceptibility to penicillin G, and one isolate was completely resistant. All five isolates that were resistant to erythromycin expressed the M phenotype. S. pyogenes exhibited high susceptibility to all other antibiotics, except tetracycline. Our study suggests that except for M. catarrhalis, all other bacterial isolates are susceptible to cephalosporins, macrolides, and fluroquinolones.

Twenty years of prospective molecular epidemiology in Senegal: changes in HIV diversity.

Over a 20-year period we have observed the dynamics of HIV-1 subtypes and HIV-2 infection in a prospective cohort of registered female sex workers (FSW) in Dakar, Senegal. Prevalence and incidence rates for HIV-1 and HIV-2 are described from 290 seroprevalent and 193 seroincident subjects who were among the 3,910 women enrolled between 1985 and 2004. We report a significant decrease of HIV-2 prevalence in the cohort, parallel to the introduction and rise of HIV-1 infection. In 328 HIV-1-infected women, a 385-bp C2-V3 fragment of the envelope gene was sequenced and classified into the following subtypes or recombinant forms: 239 (72%) were subtype A [of which 180 (55%) were CRF02_AG and 53 (16%) were A3], 10 (3%) were B, 12 (4%) were C, 11 (4%) were D, 18 (6%) were G, 24 (7%) were CRF06_cpx, and 7 (2%) were CRF09_cpx. We found an increasing proportion of CRF02_AG over many years, but recently subsubtype A3 has over-taken CRF02_AG, with the largest proportion of new infections. The predominance of existing HIV-1 subtypes did not preclude the emergence and increase of other closely related subtypes or recombinant forms. This 20-year prospective serological and sequence analysis of HIV viruses reveals a complex and changing HIV epidemic in Senegal.

Comparison of heterologous neutralizing antibody responses of human immunodeficiency virus type 1 (HIV-1)- and HIV-2-infected Senegalese patients: distinct patterns of breadth and magnitude distinguish HIV-1 and HIV-2 infections.

Neutralizing antibody responses against heterologous isolates in human immunodeficiency virus type 1 (HIV-1) and HIV-2 infections were compared, and their relationships with established clinical markers of progression were examined. Neutralizing responses against 7 heterologous primary isolates and 1 laboratory strain were compared between 32 untreated HIV-1-infected subjects and 35 untreated HIV-2-infected subjects using a pseudotyped reporter virus assay. The breadth of the neutralizing response, defined as the proportion of panel viruses positively neutralized by patient plasma, was significantly greater among HIV-2-infected subjects than among HIV-1-infected subjects. Notably, for fully one-third of HIV-2 subjects, all viruses were effectively neutralized in our panel. Magnitudes of responses, defined as reciprocal 50% inhibitory concentration (IC(50)) titers for positive reactions, were significantly greater among HIV-1-infected subjects than among HIV-2-infected subjects. When plasma samples from HIV-1 patients were tested for cross-neutralization of HIV-2 and vice versa, we found that these intertype responses are very rare and their prevalences comparable in both HIV-1 and HIV-2 infection. The significantly higher magnitude of heterologous responses for HIV-1 compared to HIV-2 prompted us to examine associations with viremia, which is known to be significantly higher in HIV-1 infection. Importantly, there was a significant positive correlation between the IC(50) titer and viral load within both the HIV-1 and HIV-2 groups, suggesting heterologous antibodies may be driven by viral replication. We conclude that HIV-2 infection is characterized by a broad, low-magnitude intratype neutralization response, while HIV-1 is characterized by a narrower but higher-magnitude intratype response and that a significant positive association between the IC(50) titer and viremia is common to both HIV-1 and HIV-2 infections.

The absence of anti-Tat antibodies is associated with risk of disease progression in HIV-2 infection.

The Tat protein of human immunodeficiency virus (HIV) is essential for viral replication and has extracellular pathogenic activity. We sought to determine whether the anti-Tat antibody response was predictive of disease progression in 144 HIV type 2 (HIV-2)-infected subjects observed longitudinally between 1985 and 2003. Sixty-eight percent of the subjects tested positive for anti-Tat antibodies, with reactivity notably established early after seroconversion and stably maintained over the course of infection. The risk and rate of progression to advanced HIV-2 AIDS was significantly higher in anti-Tat-negative subjects than in anti-Tat-positive subjects, extending the importance of this prognostic marker for HIV-2 AIDS.

Viral dynamics of primary HIV-1 infection in Senegal, West Africa.

BACKGROUND: Few studies have addressed primary human immunodeficiency virus (HIV) type 1 infection in sub-Saharan Africa, where the epidemic is of a predominantly heterosexual character and is caused by different subtypes. The present study examines the dynamics of viral replication in subjects infected with various HIV-1 subtypes. METHODS: Seven hundred fifty-two HIV-negative Senegalese women at high risk for infection were monitored every 3 months for acute/early HIV infection; 26 infections were identified (23 HIV-1 and 3 HIV-2), with an HIV-1 incidence rate of 3.23 cases/person-years observation. Multiple viral-load measurements were taken for all seroconverters. RESULTS: The mean+/-standard deviation viral load for all subjects during the early stage of infection was 4.13+/-0.66 log10 copies/mL, with an overall decrease of 0.22 log10 copies/mL after the early stage; the viral set point was reached after 12 months of infection. Most subjects had relatively low viral loads during the early stage of infection. HIV-1 CRF02_AG-infected women had a significantly higher mean viral load during the early stage of infection (mean +/- SD, 4.45+/-0.60 log(10) copies/mL) than did non-HIV-1 CRF02_AG-infected women (mean+/-SD, 3.78+/-0.46 log(10) copies/mL) (P=.008). None of the subjects reported symptoms consistent with primary HIV-1 infection. CONCLUSION: Our findings in Senegalese women differ from what have been described for primary HIV-1 infection. Further investigations of primary infections with non-B subtypes are warranted, to better characterize their differences with primary infections with subtype B.

Molecular epidemiology of human immunodeficiency virus type 1 sub-subtype A3 in Senegal from 1988 to 2001.

The global human immunodeficiency virus (HIV)epidemic is characterized by significant genetic diversity in circulating viruses. We have recently characterized a group of viruses that form a distinct sub-subtype within the subtype A radiation, which we have designated HIV type 1 (HIV-1) sub-subtype A, circulating in West Africa. A prospective study of a cohort of female sex workers (FSW) in Dakar, Senegal over an 18-year period indicated that an A3-specific sequence in the C2-V3 region of the env gene was found in 46 HIV-1-infected women. HIV-1 sub-subtype A3 appeared in the FSW population as early as 1988 and continued to be transmitted as of 2001. We also found that HIV-1 A3 is not confined to the FSW cohort in Senegal but is also circulating in the general population in Dakar. Furthermore, analyses of viral sequences from a few other West and Central African countries also demonstrated evidence of HIV-1 A3 sequence in isolates from HIV-1-infected people in Ivory Coast, Nigeria, Niger, Guinea Bissau, Benin, and Equatorial Guinea. Overall, because of the evidence of sub-subtype A3 in the general population in Senegal, as well as in a few neighboring West and Central African countries, along with the increasing incidence of infection with A3-containing viruses in the Dakar high-risk FSW population, we feel that HIV-1 sub-subtype A3 viruses are important to distinguish and monitor.

Treponemal infection rates, risk factors and pregnancy outcome in a rural area of Senegal.

A rural population of east Senegal has been under demographic surveillance for more than 30 years and a high rate of infertility has been reported. The aim of the study is to describe HIV and treponemal infection epidemiology and association with outcome of pregnancy in a population of rural Senegal. A population-based cross-sectional study was conducted among 952 randomly-selected adults of a rural community of Senegal. No participant was found to be infected with HIV, 11% had evidence of past syphilis and 5% of active syphilis. Active syphilis was associated among men with age, long-term mobility and having partners in an urban area in the last 12 months and among women with being divorced or widowed. No association was found between past or active syphilis and abortion or stillbirth but women aged 40 and more with past or active syphilis were significantly more likely to have had no history of gestation than women with no evidence of syphilis infection. In conclusion our results call for more research to understand the epidemiology of treponemal infection and to elucidate types of Treponema pallidum involved.

Comparison of HIV-1 and HIV-2 infectivity from a prospective cohort study in Senegal.

From a prospective cohort study of 1948 initially human immunodeficiency virus (HIV) uninfected female commercial sex workers followed between 1985 and 1999 in Dakar, Senegal, the authors compared the male to female per infectious sexual exposure transmission probability of HIV types one (HIV-1) and two (HIV-2). New non-parametric competing risks failure time methods were used, which minimized modelling assumptions and controlled for risk factors for HIV infection. The HIV-1 versus HIV-2 infectivity ratio over time was estimated by the ratio of smoothed non-parametric kernel estimates of the HIV-1 and HIV-2 infection hazard functions in sex workers, adjusted by an estimate of the relative HIV-1 versus HIV-2 prevalence in the partner population. HIV-1 was found to be significantly more infectious than HIV-2 throughout the follow-up period (P < 0.001). The HIV-1/HIV-2 infectivity ratio was inferred to be approximately constant over time, with estimated common value 3.55. The finding of greater HIV-1 infectivity persisted in sensitivity analyses and in covariate-adjusted analyses, with adjusted infectivity ratio estimates ranging between 3.40 and 3.86. Understanding the mechanisms by which HIV-1 infects more efficiently than HIV-2 may be useful in the development of HIV-1 vaccines. Additionally, the methodology developed here may be useful for analysing other data sets.