Pediatric tuberculosis in a high burden setting: Socio-spatial distribution, blood elements features, and outcomes.

Background: The childhood tuberculosis (TB) epidemic has been long neglected. Data on pediatric tuberculosis is needed to develop effective strategies against TB. Methods: We retrospectively reviewed 200 medical records from children aged 0-15 years who suffered from tuberculosis between 2011 and 2021 in Libreville, Gabon. We collected and analyzed socio-demographic data and clinical data. Results: 141 children files were selected (43 % girls and 57 % boys). The mean age of the patients was 9.2 years (CI: 8.5-10). Sixty per cent (60 %) of cases were from precarious housing areas, 35.34 % from mixed housing areas, and 4.51 % from residential. The cure rate was 75.24 %, 9.52 % relapsed, and 15.24 % died. Deaths were significantly higher in older children (Dunn's post-test p < 0.01). Children who recovered had higher haemoglobin and platelet counts than those who died (Dunn's test: haemoglobin p < 0.0001; thrombocytes p < 0.05). The haemoglobin threshold value of 5.5 g/dL identified children death with up to 80 % sensitivity and 86 % specificity. Thrombocytes count identified children's death with a sensitivity of 80 % and a specificity of 51 %. Conclusion: Precariousness is associated with childhood tuberculosis. The directly observed therapy (DOTS) in older children should be reinforced to limit tuberculosis-associated deaths. Haemoglobin concentration and platelet are vital prognosis markers in pediatric tuberculosis.

Time to SARS-CoV-2 clearance in African, Caucasian, and Asian ethnic groups.

BACKGROUND: COVID-19 may become a seasonal disease. SARS-CoV-2 active circulation coupled with vaccination efforts has undoubtedly modified the virus dynamic. It is therefore important investigate SARS-CoV-2 dynamic in different groups of population following the course of spatiotemporal variance and immunization. METHODS: To investigate SARS-CoV-2 clearance in different ethnic groups and the impact of immunization, we recruited 777 SARS-CoV-2-positive patients (570 Africans, 156 Caucasians, and 51 Asians). Participants were followed and regularly tested for 2 months until they had two negative tests. RESULTS: The vaccination rate was 64.6%. African individuals were less symptomatic (2%), Caucasians (41%) and Asians (36.6%). On average, viral clearance occurred after 10.5 days. Viral load at diagnosis was inversely correlated with viral clearance (p < 0.0001). The time of SARS-CoV-2 clearance was higher in Africans and Caucasians than in Asians (Dunn's test p < 0.0001 and p < 0.05, respectively). On average, viral clearance occurred within 9.5 days during the second semester (higher rate of vaccination and SARS-CoV-2 exposition), whereas it took 13.6 days during the first semester (lower rate of vaccination and SARS-CoV-2 exposition) (Mann-Whitney t-test p < 0.0001). CONCLUSION: In conclusion, ethnicity and spatiotemporal changes including SARS-CoV-2 exposition and immunization affect SARS-CoV-2 clearance.

SARS-CoV-2 Antibody Seroprevalence in Gabon: Findings from a Nationwide Household Serosurvey in a Sub-Saharan Africa Country.

Seroconversion surveys of anti-SARS-CoV-2 antibodies provide accurate estimates of the prevalence of SARS-CoV-2 infections. This nationwide population-based cross-sectional serosurvey aimed to evaluate the prevalence of SARS-CoV-2 antibodies among residents in Gabon and compare the estimated cumulative number of COVID-19 cases with the officially registered number of laboratory-confirmed cases up to December 2021. Households in each province were randomly selected. Twenty-eight localities, including sixteen urban and twelve rural, were randomly selected for the study. Whole blood samples were collected in dry tubes from all study participants nationwide within 15 days. Serum samples were used to measure SARS-CoV-2-specific ELISA titers. Overall, data from 1672 households were analyzed. Out of the 3659 participants, 3175 were found to be positive for SARS-CoV-2 antibodies, resulting in a crude seroprevalence of 86.77%. Stratification of study participants by age group showed the highest seroprevalences in the 20-29 and 40-49 age groups with 91.78% (95% CI: 89.5-93.6) and 91.42% (95% CI: 88.7-93.5), respectively. Nyanga province had the lowest prevalence (72.8%), and Estuaire and Ogooué-Lolo provinces had the highest prevalence (90 and 92%). Our results suggest a high transmission rate in the Gabonese population 21 months after the first SARS-CoV-2 case in the country. This high seroprevalence estimate could indicate that the population may not have adequately implemented or appropriately adhered to the applied infection control measures.

Changes of C-reactive protein and Procalcitonin after four weeks of treatment in patients with pulmonary TB.

Objective: Tuberculosis (TB) remains a public health concern worldwide, affecting millions of people every year. Detailed characterization of disease pathophysiology is key to proper diagnosis, disease progression, or treatment follow-up and evaluation. The present study investigated C-reactive protein and Procalcitonin (PCT) as candidate markers of early treatment response and disease activity. Methods: From September to December 2019, 21 HIV-negative consecutive TB patients were recruited, within the setting of the Gabonese TB specialized hospital and the National Laboratory of Public Health, in a prospective study. CRP and PCT levels were measured by chemiluminescence at diagnosis and 4 weeks following the initiation of anti-TB treatment. Results: The mean concentration of CRP in TB patients was 114.7 mg/L (95 % CI: [83.8-145.6]) at diagnosis and 20.2 mg/L (95 % CI: [14.1-26.4]) 4 weeks following anti-TB treatment. The drop in CRP concentrations between diagnosis, and week 4 following anti-TB treatment showed was significant (p < 0.0001). The average concentration of PCT at the time of diagnosis was 0.3 ng/mL (95 % CI: [0.19-0.41]). PCT Concentration dropped below 0.05 ng/mL 4 weeks following the start of anti-TB treatment (p < 0.01). Conclusion: CRP and PCT are potential TB biomarkers, each, carrying important keys. If the drop in both proteins may indicate a significant reduction of the Mtb burden, the maintenance of CRP above the inflammation threshold could indicate the presence of residual bacilli. However, the clinical translation of the present finding will require more investigation.

Allergen sensitization and polysensitization pattern of adults and children in an urban Sub-Saharan African setting (Libreville, Gabon).

Background: It is believed that allergic diseases are increasing in Africa. However, the health sector in Africa has yet to catch up with this paradigm shift. We looked at the number of patients referred to us for allergy testing and investigated allergen sensitization. Methods: A retrospective analysis was done on 97 serum allergen-specific IgE results collected from patients suspected of having allergies in Libreville from 2018 to 2021. Specific IgE responses to 180 allergens were investigated. The general sensitization patterns were analyzed. Also analyzed were sensitization patterns for adults and children. The difference in the IgE-binding allergen positivity rate between groups was calculated by using the chi-square (χ2) test. Results: The allergens most commonly causing sensitization were from mites (65%), barley (48%), peach (48%), dog and/or cat dander (44%), house dust (44%), peanut (39%), tomato (39%), cockroach (37%), crab (36%), garlic and/or onion (34%), rye (34%), egg white (32%), shrimp (32%), kiwi (32%), soya bean (32%), citrus mix (29%), cheese (27%), milk (27%), walnut (27%), ox-eye daisy (24%) and orchard grass (24%). Moreover, 60% of patients (36 of 60) were polysensitized to inhalant allergens, 53% (31 of 58) were polysensitized to food allergens, and 29% (14 of 48) were polysensitized to inhalant and food allergens; 65% of patients (53 of 81) were sensitized to allergens originating from mites, fungi (including Candida albicans, Alternaria alternata, Aspergillus fumigatus, Cladosporium herbarum, and Pennicillium notatum), or bacteria (staphylococcal enterotoxin B). Conclusions: The sensitization pattern of allergens in our setting is rich and varied, with a high prevalence of polysensitization.

Circulating anti-SARS-CoV-2 nucleocapsid (N)-protein antibodies and anti-SARS-CoV-2 spike (S)-protein antibodies in an African setting: herd immunity, not there yet!

OBJECTIVE: Herd immunity is achieved when in a population, immune individuals are in a sufficiently large proportion. Neutralizing antibodies specific to SARS-CoV-2 that are produced following infection or vaccination are critical for controlling the spread of COVID-19. The objective of the present work was to investigate the rate of SARS-CoV-2 natural immunization in Gabonese. RESULTS: One thousand, four hundred and ninety two people were enrolled. The overall prevalence of anti-SARS-CoV-2 antibodies was 36.2%. Moreover, 76.4% of people who developed a humoral response to SARS-CoV-2 produced both anti-SARS-CoV-2 N-protein antibodies and anti-SARS-CoV-2 S-protein antibodies, which correspond to 27.7% of the total population. In infants (0-9 month), children (1-17 years) and adults, the prevalence of anti-SARS-CoV-2 antibodies was relatively the same, between 33 and 37% (any antibody types) and between 25 and 28.6% (neutralizing antibodies). In this African context, one-third (1/3) of the screened population was exposed to SARS-CoV-2 and three-quarter (3/4) of those exposed individuals developed neutralizing antibodies against SARS-CoV-2. This data suggest that herd immunity is not yet to be achieved in Gabon.

Evidence and implications of pre-existing humoral cross-reactive immunity to SARS-CoV-2.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged throughout the world. Building knowledge around Covid-19 is crucial to devise facts based approaches to respond efficiently against this pandemic. AIM: We aimed to investigate pre-existing humoral cross-reactive immunity to SARS-CoV-2. METHOD: We have tested the reactivity against SARS-CoV-2 nucleocapsid (N) antigen of sera collected from healthy healthcare volunteers in 2014. We assessed immunoglobulins reactive against SARS-CoV-2 N-antigen using a well-validated serological platform; Elecsys assay. RESULTS: Sera from 32 subjects (out of 135 [23.7%]) were reactive to SARS-CoV-2 N-antigen, suggesting the presence of anti-SARS-CoV-2 N-antigen antibodies. CONCLUSION: Although the clinical relevance of the observed reactivity can only be speculated and needs to be investigated, the implication of this finding for coronavirus disease 2019 seroepidemiological survey and vaccines' clinical trials is critical.

Dynamic and features of SARS-CoV-2 infection in Gabon.

In a context where SARS-CoV-2 population-wide testing is implemented, clinical features and antibody response in those infected have never been documented in Africa. Yet, the information provided by analyzing data from population-wide testing is critical to understand the infection dynamics and devise control strategies. We described clinical features and assessed antibody response in people screened for SARS-CoV-2 infection. We analyzed data from a cohort of 3464 people that we molecularly screened for SARS-CoV-2 infection in our routine activity. We recorded people SARS-CoV-2 diagnosis, age, gender, blood types, white blood cells (WBC), symptoms, chronic disease status and time to SARS-CoV-2 RT-PCR conversion from positive to negative. We calculated the age-based distribution of SARS-CoV-2 infection, analyzed the proportion and the spectrum of COVID-19 severity. Furthermore, in a nested sub-study, we screened 83 COVID-19 patients and 319 contact-cases for anti-SARS-CoV-2 antibodies. Males and females accounted for respectively 51% and 49% of people screened. The studied population median and mean age were both 39 years. 592 out of 3464 people (17.2%) were diagnosed with SARS-CoV-2 infection with males and females representing, respectively, 53% and 47%. The median and mean ages of SARS-CoV-2 infected subjects were 37 and 38 years respectively. The lowest rate of infection (8%) was observed in the elderly (aged > 60). The rate of SARS-Cov-2 infection in both young (18-35 years old) and middle-aged adults (36-60 years old) was around 20%. The analysis of SARS-CoV-2 infection age distribution showed that middle-aged adults accounted for 54.7% of SARS-CoV-2 positive persons, followed respectively by young adults (33.7%), children (7.7%) and elderly (3.8%). 68% (N = 402) of SARS-CoV-2 infected persons were asymptomatic, 26.3% (N = 156) had influenza-like symptoms, 2.7% (N = 16) had influenza-like symptoms associated with anosmia and ageusia, 2% (N = 11) had dyspnea and 1% (N = 7) had respiratory failure, which resulted in death. Data also showed that 12% of SARS-CoV-2 infected subjects, had chronic diseases. Hypertension, diabetes, and asthma were the top concurrent chronic diseases representing respectively 58%, 25% and 12% of recorded chronic diseases. Half of SARS-CoV-2 RT-PCR positive patients were cured within 14 days following the initiation of the anti-COVID-19 treatment protocol. 78.3% of COVID-19 patients and 55% of SARS-CoV-2 RT-PCR confirmed negative contact-cases were positive for anti-SARS-CoV-2 antibodies. Patients with severe-to-critical illness have higher leukocytes, higher neutrophils and lower lymphocyte counts contrarily to asymptomatic patients and patients with mild-to-moderate illness. Neutrophilic leukopenia was more prevalent in asymptomatic patients and patients with mild-to-moderate disease for 4 weeks after diagnosis (27.1-42.1%). In Patients with severe-to-critical illness, neutrophilic leukocytosis or neutrophilia (35.6-50%) and lymphocytopenia (20-40%) were more frequent. More than 60% of participants were blood type O. It is also important to note that infection rate was slightly higher among A and B blood types compared with type O. In this African setting, young and middle-aged adults are most likely driving community transmission of COVID-19. The rate of critical disease is relatively low. The high rate of anti-SARS-CoV-2 antibodies observed in SARS-CoV-2 RT-PCR negative contact cases suggests that subclinical infection may have been overlooked in our setting.

Increased platelets count in HIV-1 uninfected infants born from HIV-1 infected mothers.

HIV-exposed uninfected infants (HEU) represent a growing population in developing countries including Gabon. Several studies have shown the vulnerability of these infants toward infectious diseases. The aim of the study was to contribute to the global effort to understand how HIVexposure or anti retroviral therapy affects infants' blood elements. We assessed HEU infants' complete blood count using a blood analyzer instrument. Our investigations showed that among the observed clinically relevant hematological abnormalities events, thrombocytosis was the most prevalent clinically relevant hematological abnormality associated with HEU infants'. We showed that HEU infants had significantly higher platelets count than HUinfants. Therefore, higher level of platelets seems to characterize HEU infants when compared to HU infants.

Detection of novel astroviruses among rodents of Gabon, Central Africa.

Astroviruses (AstVs) are mostly responsible for mild to severe gastroenteritis infections in humans and animals. AstVs infect a wide range of host species, have a large genetic diversity with different circulating variants and are thus a high zoonotic risk for human populations. Among these host species, rodents are known to harbor several AstVs variants. Therefore, it is important to identify in rodent species which AstVs are circulating and evaluate their potential zoonotic risk for humans. In this context, this study aimed to screen the presence of AstVs in 267 rodents trapped in 2012 in Franceville and Makokou, two cities in Gabon. RNA extracted from grinded intestines were used for the screening of AstVs by amplification of a conserved region of the RNA dependent RNA polymerase. Results report the identification of AstVs in 12 individuals (4.6% rate), belonging to three different species including Rattus rattus, Mus musculus and Hybomys univittatus. These findings report the first identification of AstVs in R. rattus and H. univittatus. The phylogenetic analyses indicate host specificity of rodents AstVs. The absence of rodent AstVs within the human AstV clade suggests a low rate of interspecies transmission of these viruses and consequently a low zoonotic risk.

M. tuberculosis infection and antigen specific cytokine response in healthcare workers frequently exposed to tuberculosis.

Tuberculosis (TB) is the leading cause of death due to an infectious agent, but only a small fraction of those infected develop the disease. Cytokines are involved in the mediation and regulation of immunity, and their secretion patterns may reflect the infection status. To increase our understanding of immune response to M. tuberculosis infection, we conducted a cross-sectional study investigating M. tuberculosis infection status and comparing the release profiles of cytokines GM-CSF, IFN-γ, IL-1ß, IL-10, IL-12 (p70), IL-2, IL-4, IL-5, IL-6, IL-8, TNF-α, in community controls (CCs) and healthy healthcare workers (HCWs) highly exposed to TB. Among HCWs and CCs, the probability of latent M. tuberculosis (LTB+) infection was respectively 5.4 (p = 0.002) and 3.4 (p = 0.006) times higher in men than women. The odds ratio of LTB infection was 4 times higher among HCWs in direct contact with active TB patients than other HCW (p = 0.01). Whole blood supernatant cytokine responses to M. tuberculosis antigens showed differential pro-inflammatory responses between HCWs and CCs. CCsLTB- had higher IL-1ß responses than HCWsLTB- (p = 0.002). HCWsLTB+ had significantly higher IL-8 responses to M. tuberculosis antigens than HCWsLTB- (p = 0.003) and CCsLTB- (p = 0.015). HCWsLTB+/- showed weak but positive TNF-α responses to M. tuberculosis antigen stimulation compared to CCsLTB+/- (p ≤ 0.015). Looking at T-helper (1 and 2) responses, HCWsLTB+ and CCsLTB+ had significantly higher IFN-γ and IL-2 responses compared to HCWsLTB- and CCsLTB- (p < [0.0001-0.003]). Also, TB antigen induced IL-5 secretion was significantly higher in HCWsLTB+ and CCsLTB+ than in non-infected CCsLTB- (p < [0.005-0.04]). M. tuberculosis antigen specific responses in HCWsLTB+ varied based on active TB exposure gradient. HCWsLTB+ who were highly exposed to active TB (≥3 hours per day) had significantly higher IFN-γ and IL-8 responses (p ≤ 0.02) than HCWs LTB+ not in direct contact with active TB patients. HCWsLTB+ working with active TB patients for 5 to 31 years had a significantly enhanced secretion of proinflammatory cytokines (GM-CSF, IFN-γ, IL-1ß, IL-2, IL-6, IL-8, IL-12p70, TNF-α) compared to HCWsLTB- (p < [0.0001-0.01]). Secretion of anti-inflammatory/Th2 cytokines IL-5 and IL-10 was also higher in HCWsLTB+ than HCWsLTB-. In conclusion, LTBI individuals controlling the M. tuberculosis infection have an enhanced TB specific Th1-cytokines/proinflammatory response combined with selected Th2 type/anti-inflammatory cytokines induction.

Publisher Correction: M. tuberculosis infection and antigen specific cytokine response in healthcare workers frequently exposed to tuberculosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Altered Toll-Like Receptor-4 Response to Lipopolysaccharides in Infants Exposed to HIV-1 and Its Preventive Therapy.

Pathogen sensing and recognition through pattern recognition receptors, and subsequent production of pro-inflammatory cytokines, is the cornerstone of the innate immune system. Despite the fact that HIV-exposed uninfected (HEU) infants are prone to serious bacterial infections, no study has focused on the functionality of their bacteria recognition system. This is the first study to investigate baseline levels of three critically important immune response molecules in this population: complement component (C)-3, toll-like receptor (TLR)-4, and C-reactive protein (CRP). We enrolled 16 HEU and 6 HIV-unexposed (HU) infants. TLR4 function was investigated by stimulating whole blood with increasing concentrations of TLR4-agonist ultrapure lipopolysaccharides. TLR4/TLR4-agonist dose response were assessed by measuring IL-6 secretion. Complement C3 and CRP were measured by photo spectrometry. Data showed no significant differences in baseline concentration of CRP between HEU and HU infants. Complement C3 was significantly higher in HEU infants than HU infants. TLR4 anergy was observed in 7 of 12 HEU infants, whereas the rest of HEU infants (n = 4) and the control HU infants tested (n = 3) showed responsive TLR4. None of the HEU infants investigated in this study had severe infections in the year after their birth. In conclusion, TLR4 anergy can occur in HEU infants without necessarily translating to increased vulnerability to infectious diseases.

Cases of Impaired Oxidative Burst in HIV-Exposed Uninfected Infants' Neutrophils-A Pilot Study.

An increased risk of serious bacterial infections in HIV-exposed uninfected (HEU) infants has been demonstrated. Although neutrophils are essential for the protection of infants against bacterial infections, no study has investigated their profile in HEU infants to date. In this study, we assessed the function of neutrophils in HEU infants using the nitroblue tetrazolium reduction test. Among 25 HEU infants, 9 (36%) showed a reduced ability of their neutrophils to produce reactive oxygen species upon stimulation with bacteria. No alteration of total neutrophil counts was noted in the blood of HEU infants indicating that the alteration observed in the 36% of HEU infants may only be functional. Conclusively, impaired neutrophil function could be a factor of vulnerability in HEU infants.