Meningococcal disease is caused by the bacterium Neisseria meningitidis, which is a commensal in the human upper airways. Teenagers and young adults are the main reservoir for the bacteria. The aim of this study was to assess the prevalence of meningococcal carriage and risk factors for carriage among high school and university students in Northwestern Ethiopia. Oropharyngeal swabs and buccal samples were collected and stored on Whatman FTA-cards pending PCR analysis. DNA was extracted and a Multiplex TaqMan® custom assay was performed to detect N. meningitidis bacteria using the genes sodC and porA as species-specific targets. Genogrouping was performed for the samples positive for N. meningitidis using multiplex real-time PCR for the groups A, B, C, W, Y and X using a Rotor-Gene Q real-time PCR system. Out of the 1025 participants, 52

BACKGROUND:This study evaluated the cost of the vaccine-preventable diseases (VPD) surveillance system in Ethiopia to inform budgeting for disease detection, prevention, and control, and planning for transitions from donor funding. METHODS:This cross-sectional retrospective, bottom-up micro-costing study collected data on resource utilization to conduct VPD surveillance during one fiscal year (2018-2019) in Ethiopia. The study covered 16 VPDs and costs from the government and partners perspective. RESULTS:The estimated economic costs of VPD surveillance in Ethiopia were US$69.11 million or US$0.70 per capita, while financial costs were US$26.83 million or US$0.27 per capita. The largest economic cost was for labor (41.0%) and the largest financial cost was for supplies (36.9%). Resources were mostly allocated to integrated, general disease surveillance (economic: 54.6%; financial: 50.7%), followed by surveillance for measles and rubella (economic: 15.9%; financial: 22.5%) and polio (economic: 12.4%; financial: 15.7%). The main funder was the Ethiopian Ministry of Health (economic: 78.8%; financial 62.6%), including donor resources channeled through the ministry. CONCLUSIONS:Human resources were primary drivers of economic costs. Although the Ethiopian VPD surveillance system uses shared resources across multiple VPDs, resulting in scale efficiencies, and the Ethiopian government covers most of its economic costs, a substantial portion relies on direct external donor support.

[This corrects the article DOI: 10.1371/journal.pgph.0004407.].

Assessing COVID-19 burden through clinical surveillance is suboptimal, as individuals with mild or no symptoms rarely seek care. Seroprevalence studies overcome this limitation by capturing both symptomatic and asymptomatic infections, providing accurate estimates of community transmission, immunity gaps, and epidemic progression. This is critical for informing public health strategies, especially in resource-limited settings like Ethiopia post-vaccine rollout. To estimate the national seroprevalence of SARS-CoV-2 antibodies in Ethiopia after widespread vaccine deployments. A population-based cross-sectional study was conducted using stratified three-stage cluster sampling across 11 regions (excluding Tigray). We enrolled 14,074 participants (99

Most African countries, including Ethiopia, have not developed local well-defined reference intervals (RIs) for immuno-hematological testes in terms of pregnant women. As a result, we were using reference intervals derived from non-Africans. This is not appropriate because CD4 + T cell counts (CD4 count) are affected by several factors including ethnic and environmental factors. Therefore, this study aimed to develop reference interval for CD4 count for apparently healthy pregnant women in Addis Ababa, Ethiopia. After excluding six pregnant women who did not pass the screening tests, 156 apparently healthy pregnant women who were 18–49 years old were included in the final analysis. The medians of CD4 absolute counts and CD4

BACKGROUND:The COVID-19 pandemic highlighted SARS-CoV-2 variants with increased transmissibility and immune evasion. In Ethiopia, where cases surged, the understanding of the virus's dynamics was limited. This study analyzed SARS-CoV-2 variants during the fifth wave, crucial for guiding vaccines, therapeutics, diagnostics, and understanding disease severity. METHOD:From June to August 2022, 150 SARS-CoV-2-positive samples were randomly selected from the Ethiopian Public Health Institute repository. Sixty-three high-quality genome sequences were analyzed. RESULTS:Of the 63 sequences, 70% were from males and 30% from females, with a median age of 34. Omicron dominated (97%, 61/63), primarily clade 22A (64%, 40/63), followed by 22B (18%, 11/63) and 21K (14%, 9/63). Delta accounted for 3.2% (2/63). Omicron was identified in all (25) vaccinated study participants. Ethiopian sequences showed limited evolutionary divergence and lower genetic diversity compared to global sequences. CONCLUSION:Omicron was the predominant variant during Ethiopia's fifth wave, indicating recent community transmission. Despite minor genetic diversity differences, ongoing surveillance remains critical for tracking variants and informing public health interventions.

Introduction: There is limited information about vaccine-preventable disease (VPD) surveillance cost. To address this gap, retrospective micro-costing studies of pre-COVID-19 pandemic VPD surveillance were conducted in Nepal and Ethiopia. Based on these evaluations-the sole cost evaluations on comprehensive VPD surveillance-this article provides methodological considerations and recommendations for other countries planning to conduct VPD surveillance costing studies to inform planning and budgeting. Methods: The methods used for each study were systematically compared by key themes: costing perspective, cost categories, costing approach, allocation of shared costs, sampling criteria, extrapolation strategies, data collection, and analytic adjustments. For each theme, investigators identified methodologic challenges and potential strategies to address them, compared study methodologies to surveillance costing guidelines, and recommended practices for future such studies. Results: The studies used similar perspectives and VPD inclusion criteria. Costs in Nepal were collected and analyzed by a subset of surveillance core and support functions, whereas the Ethiopia study categorized costs using surveillance support functions from the Global Strategy on Comprehensive VPD Surveillance. A mix of random and purposive sampling of surveillance sites was used in both studies. Surveillance sites were selected considering the strata of interest at each administrative level. Results from both studies were extrapolated country-wide using sampling weights and assumptions about the representativeness of purposively sampled units. Discussion: The review highlighted potential methodologic tradeoffs in utility and precision of results based on the lessons learned from two country VPD surveillance cost studies. The advantages of collecting and using cost estimates by VPD surveillance core versus support function for program budgeting for varied audiences should be explored in future studies. Sampling strategies should be developed with consideration for the precision needed for the intended use of costing results. The resulting recommendations can improve and standardize the conduct and interpretation of future such studies.

Background:Bacterial meningitis (BM) represents the most severe variant of meningitis, with a mortality rate that may reach up to 100% in the absence of appropriate treatment. The success of therapeutic interventions is depends upon prompt and precise diagnostic evaluations. However, there exists a significant deficiency in the literature regarding the diagnostic efficacy within the Ethiopian context. Consequently, this study aims to evaluate and compare the diagnostic precision of microbial culture and polymerase chain reaction (PCR) methodologies in individuals with suspected meningitis in Northwest Ethiopia. Methods:Cerebrospinal fluid (CSF) samples were procured from 400 patients who were clinically suspected of having meningitis and were admitted to the University of Gondar Specialized Hospital (UoGSH), located in Northwest Ethiopia. Real-time PCR, microbial culture, Gram staining, and cell enumeration were conducted at both the UoGSH laboratory and the Armauer Hansen Research Institute in Addis Ababa. Results:Of the total patients enrolled in the study, 58% were male. Clinical manifestations such as fever, headache, and neck stiffness were reported in 94%, 90%, and 81% of the patients, respectively, whereas altered consciousness was recorded in 37% of the cohort. The real-time PCR methodology identified 38 patients (10%) as positive for meningitis, in contrast to microbial culture, which detected only 10 (3%) of these positive cases. The two diagnostic modalities exhibited a correlation coefficient of 0.4 (p < 0.05). Conclusion:The traditional microbiological culture technique, in conjunction with Gram staining, was found to have a limited sensitivity in identifying bacterial meningitis compared with the real-time PCR methodology. Consequently, the integration of molecular approaches with higher sensitivity, such as real-time PCR, facilitates prompt diagnosis and precise treatment, while simultaneously sustaining the overarching meningitis surveillance framework.

Diarrheal illness remains a major global health challenge, causing millions of deaths annually. Non-typhoidal Salmonella (NTS), Shiga toxin-producing Escherichia coli (STEC), and Campylobacter species (CAMPY) significantly contribute to this burden. Given the limited information on these pathogens in Ethiopia, this study aimed to estimate their prevalence among diarrhea patients in Ethiopia and identify risk factors for infection. A cross-sectional study was conducted from October 2021 to November 2022 in three hospitals in Ethiopia (Addis Ababa, Gondar, and Harar). Sociodemographic characteristics, clinical signs and symptoms were collected from study participants using a structured questionnaire. Stool samples were tested for NTS, STEC, and CAMPY using standardized methods. The prevalence of targeted pathogens was estimated overall and by study sites. Univariable and multivariable logistic regression were used to identify associated factors. A total of 2,331 patients were enrolled. The overall prevalence of NTS, STEC (stx only), STEC (stx + eae), and CAMPY was 1.29% (95%CI: 0.91, 1.84), 12.56% (95%CI: 11.29, 13.98), 3.43% (95%CI: 2.77, 4.25), and 4.46% (95%CI: 4.61, 8.00), respectively. Harar had the highest prevalence of all the pathogens compared to Addis Ababa and Gondar. Odds of NTS in Harar were over 10 (AOR: 10.43: 95%CI: 2.95, 69.20) and 3.5 times (AOR: 3.57: 95%CI: 1.50, 9.90) higher than that in Addis Ababa and Gondar, respectively. Odds of STEC (stx only) in the dry (AOR: 1.97: 95%CI: 1.37, 2.90) and long rainy (AOR: 1.80: 95%CI: 1.20, 2.69) seasons were nearly twice the odds in the short rainy season. Odds of CAMPY infection decreased by 3.29% (AOR: 0.97: 95%CI: 0.95, 0.98) with every one-year increase in age. Moreover, the odds of CAMPY infection for rural residents (AOR: 1.93, 95%CI: 1.15, 3.19) were nearly twice that of urban residents. This is the first study to estimate the prevalence of NTS, STEC, and CAMPY simultaneously across all age groups and diverse regions in Ethiopia, revealing significant variations. Results can be used to understand the burden of disease, inform clinical management and risk mitigation strategies to reduce illness in Ethiopia.

SARS-CoV-2 co-infection with the influenza virus or human respiratory syncytial virus (RSV) may complicate its progress and clinical outcomes. However, data on the co-detection of SARS-CoV-2 with other respiratory viruses are limited in Ethiopia and other parts of Africa to inform evidence-based response and decision-making. We analyzed 4,989 patients' data captured from the national severe acute respiratory illness (SARI) and influenza-like illness (ILI) sentinel surveillance sites over 18 months period from January 01, 2021, to June 30, 2022. Laboratory specimens were collected from the patients and tested for viral respiratory pathogens by real-time, reverse transcription polymerase chain reaction (RT-PCR) at the national influenza center. The median age of the patients was 14 years (IQR: 1-35 years), with a slight preponderance of them being at the age of 15 to less than 50 years. SARS-CoV-2 was detected among 459 (9.2%, 95% CI: 8.4-10.0) patients, and 64 (1.3%, 95% CI: 1.0-1.6) of SARS-CoV-2 were co-detected either with Influenza virus (54.7%) or RSV (32.8%) and 12.5% were detected with both of the viruses. A substantial proportion (54.7%) of SARS-CoV-2 co-detection with other respiratory viruses was identified among patients in the age group from 15 to less than 50 years. The multivariable analysis found that the odds of SARS-CoV-2 co-detection was higher among individuals with the age category of 20 to 39 years as compared to those less than 20 years old (AOR: 1.98, 95%CI:1.15-3.42) while the odds of SARS-CoV-2 co-detection was lower among cases from other regions of the country as compared to those from Addis Ababa (AOR:0.16 95%CI:0.07-0.34). Although the SARS-CoV-2 co-detection with other respiratory viral pathogens was minimal, the findings of this study underscore that it is critical to continuously monitor the co-infections to reduce transmission and improve patient outcomes, particularly among the youth and patients with ILI.

The severity of infectious disease outcomes is dependent on the virulence factors of the pathogen and the host immune response. CARD8 is a major regulator of the innate immune proinflammatory response and has been suggested to modulate the host response to common inflammatory diseases. In the present study, the C10X genetic polymorphism in the CARD8 gene was investigated in relation to bacterial meningitis. A total of 400 clinically suspected meningitis patients hospitalized at the University of Gondar Hospital were enrolled in the study. Cerebrospinal fluid (CSF) and blood samples were collected for laboratory investigations. The collected CSF was cultured, and all the results obtained from the culture were confirmed using direct RT‒PCR. Genotyping of whole-blood samples was performed using a TaqMan assay. The results were compared with apparently healthy controls and with PCR-negative meningitis suspected patients. Of the included patients, 57

Antimicrobial resistance (AMR) is designated as a global health crisis by the United Nations. In 2019, an estimated 4.95 million deaths were associated with AMR globally. The increasing global spread of resistant pathogens is a major threat to global health security (GHS). AMR has economic, social, and political ramifications worldwide with a disproportionate burden on resource-limited countries. Despite the growing concern over AMR globally, there are multiple challenges to bridge the gap between policies and practices. A strong interface among the human, animal, and environment through One Health approach is crucial to combat AMR effectively. There is a need to strengthen AMR surveillance, improve laboratory diagnostic capacity, initiate antimicrobial stewardship, reinforce infection prevention, and control programs in both humans and veterinary medicine. Effective implementation of national action plans that includes the human, animal, and environmental aspects with engagement of local, national, and intergovernmental organizations/partners is needed. Moreover, it is critical to invest in research and development of new antimicrobials and alternatives such as vaccines, to increase awareness and education, and to promote regulatory capacities for prevention, detection, and response to AMR at local, regional, and global levels.

Delayed detection in TB due to structural and diagnostic shortcomings is pivotal for disease transmission, morbidity and mortality. We investigated whether an inclusive screening, followed by a structured clinical follow-up (FU) could improve case-finding.Patients were recruited from health centres in Bissau, Guinea-Bissau, and Gondar, Ethiopia. A routine FU was done at Week 2. If persisting symptoms were found, patients were investigated using chest X-ray (CXR) and Xpert® MTB/RIF, followed by a medical consultation. The main outcome were additional TB patients diagnosed by applying the FU strategy.Of 3,571 adults, 3,285 (95%) were examined at Week 2 FU, where 2,491 (72%) were asymptomatic. Screening patients presenting with cough >2 weeks alone contributed to the diagnosis of 93 patients (45% of all patients diagnosed here), whereas a TBscore >3 increased this by 18 (9%); adding a Week 2 FU yielded an additional 94 (46%) patients. Among the 794 (24%) with persisting symptoms, 25 were diagnosed using Xpert and 69 at clinical FU, which constituted 46% (94/205) of the total TB patients diagnosed.A Week 2 FU visit, which can be nested into routine healthcare, increased the diagnosis of TB patients by two-fold and avoids diagnostic gaps in the cascade-of-care..

Objectives: Acute respiratory infections because of respiratory syncytial viruses (RSVs) are among the major leading causes of morbidity and mortality in children worldwide. RSV prevalence and its contributing factors among children aged under 5 years in Ethiopia are not well studied. To assess the prevalence and associated factors of RSV infection in children aged under 5 years using influenza sentinel surveillance sites in Ethiopia. Methods: A cross-sectional study design was used utilizing influenza -like illness/sever acute respiratory illness surveillance data from January 2021 to December 2022 at the Ethiopian Public Health Institute. Results: In total, 2234 cases were included, with an overall RSV positivity rate of 16.2%. The RSV positivity rate was high in children aged under 1 year (22.8%) and during fall season (24.8%). The RSV positivity rate was significantly associated with ages under 1 year (adjusted odds ratio [AOR] 2.8, 95% confidence interval [CI]: 1.89-4.15) and 1-2 years (AOR 1.9, 95% CI: 1.26-2.73) and the fall season (AOR 1.67, 95% CI: 1.17-2.38). Conclusion: The study revealed that a considerably high RSV positivity rate was detected in children aged under 5 years. The age of children and season have a significant association with RSV positivity rate. Further studies of RSV viral genotype, clinical characteristics, and disease outcome need to be conducted for a better understanding of the virus and disease outcome.

Background:There is a need to build research capacity to improve maternal, newborn, and child health (MNCH) in low- and middle-income countries (LMICs). To address this gap, we co-designed the HaSET (meaning 'happiness' in Amharic) MNCH Research Fellowship programme for academics and policymakers in collaboration with the Ministry of Health (MOH) and academic institutions in Ethiopia. Methods:Based on interviews and focus group discussions regarding a landscape analysis of the MNCH research environment, we developed an innovative 'learning by doing' model in which fellows identified research questions, developed proposals, obtained institutional review board (IRB) approvals, conducted research, analysed data, disseminated their findings, and developed policy briefs. Postdoctoral fellows were paired with policymakers and health professionals at the MoH to facilitate the translation of research findings into policy and programmes. Each pair received mentorship from a member of the HaSET's scientific advisory group (SAG) who had expertise in research methods, data analysis, dissemination, and translation of evidence into policy. Results:The HaSET MNCH Research Fellowship curriculum included 10 modules covering topics from biostatistics to study operations and professional development. From March 2021 to July 2023, five postdoctoral fellows from local universities and four policymakers from the MoH and government research institutes underwent the HaSET programme, where they learned to gather high-quality evidence on priority research questions and guide the implementation of national policies and programmes. Leveraging existing data, the fellows produced 15 manuscripts and 11 policy briefs. The programme established a functional research link between the MoH, regional health bureaus, and local universities, while utilising the SAG's expertise in mentorship. Conclusions:This robust and comprehensive HaSET MNCH Research Fellowship produced the first cohort of dedicated fellows trained in evidence-based medicine and mentored them to become effective public health professionals. They conducted high-quality studies to inform policy decisions on MNCH interventions in Ethiopia. Given its sustainability and scalability, researchers and academic institutions can further adapt the fellowship curriculum within capacity-building programmes to educate the next generation of research leaders in LMICs.

BACKGROUND:The COVID-19 pandemic is one of the most devastating public health emergencies of international concern to have occurred in the past century. To ensure a safe, scalable, and sustainable response, it is imperative to understand the burden of disease, epidemiological trends, and responses to activities that have already been implemented. We aimed to analyze how COVID-19 tests, cases, and deaths varied by time and region in the general population and healthcare workers (HCWs) in Ethiopia.METHODS:COVID-19 data were captured between October 01, 2021, and September 30, 2022, in 64 systematically selected health facilities throughout Ethiopia. The number of health facilities included in the study was proportionally allocated to the regional states of Ethiopia. Data were captured by standardized tools and formats. Analysis of COVID-19 testing performed, cases detected, and deaths registered by region and time was carried out.RESULTS:We analyzed 215,024 individuals' data that were captured through COVID-19 surveillance in Ethiopia. Of the 215,024 total tests, 18,964 COVID-19 cases (8.8%, 95% CI: 8.7%- 9.0%) were identified and 534 (2.8%, 95% CI: 2.6%- 3.1%) were deceased. The positivity rate ranged from 1% in the Afar region to 15% in the Sidama region. Eight (1.2%, 95% CI: 0.4%- 2.0%) HCWs died out of 664 infected HCWs, of which 81.5% were from Addis Ababa. Three waves of outbreaks were detected during the analysis period, with the highest positivity rate of 35% during the Omicron period and the highest rate of ICU beds and mechanical ventilators (38%) occupied by COVID-19 patients during the Delta period.CONCLUSIONS:The temporal and regional variations in COVID-19 cases and deaths in Ethiopia underscore the need for concerted efforts to address the disparities in the COVID-19 surveillance and response system. These lessons should be critically considered during the integration of the COVID-19 surveillance system into the routine surveillance system.

Epstein–Barr virus (EBV) is a well-known risk factor for the development of nasopharyngeal carcinoma, Hodgkin’s lymphoma (HL), and Non-Hodgkin’s lymphoma (NHL). People with HIV infection (PWH) are at increased risk for EBV-associated malignancies such as HL and NHL. Nevertheless, there are limited data on the burden of EBV among this population group in Ethiopia. Hence, this study aimed to determine the burden of EBV infection among adult HIV-positive individuals in Ethiopia and assess the determinants of EBV DNA positivity. We conducted a cross-sectional study at the Tikur Anbessa Specialised Hospital from March 2020 to March 2021. Two hundred and sixty individuals were enrolled in this study, including 179 HIV-positive and 81 HIV-negative individuals. A structured questionnaire was used to capture demographic and individual attributes. In addition, the clinical data of patients were also retrieved from clinical records. EBV viral capsid antigen (VCA) IgG antibody was measured by multiplex flow immunoassay, and EBV DNA levels were tested by quantitative real-time polymerase chain reaction (q-PCR) assays targeting the EBNA-1 open reading frame (ORF). Descriptive statistics were conducted to assess each study variable. A multivariable logistic regression model was applied to evaluate the determinants of EBV infection. Statistical significance was determined at a p-value < 0.05. Two hundred and fifty-three (97.7%) study participants were seropositive for the EBV VCA IgG antibody. Disaggregated by HIV status, 99.4% of HIV-positive and 93.8% of HIV-negative participants were EBV seropositive. In this study, 49.7% of HIV-positive and 24.7% of HIV-negative individuals were EBV DNA positive. PWH had a higher risk of EBV DNA positivity at 3.05 times (AOR: 3.05, 95% CI: 1.40–6.67). Moreover, among PWH, those with an HIV viral load greater than 1000 RNA copies/mL (AOR = 5.81, 95% CI = 1.40, 24.13) had a higher likelihood of EBV DNA positivity. The prevalence of EBV among PWH was significantly higher than among HIV-negative individuals. Higher HIV viral loads in PWH were associated with an increased risk of EBV DNA positivity. Since the increases in the viral load of EBV DNA among PWH could be related to the risk of developing EBV-associated cancers, it is necessary for more research on the role of EBV in EBV-associated cancer in this population group to be carried out.

Background Child mortality is high in Ethiopia, but reliable data on the causes of death are scarce. We aimed to gather data for the contributory causes of stillbirth and child deaths in eastern Ethiopia. Methods In this population-based post-mortem study, we established a death-notification system in health facilities and in the community in Kersa (rural), Haramaya (rural) and Harar (urban) in eastern Ethiopia, at a new site of the Child Health and Mortality Prevention Surveillance (CHAMPS) network. We collected ante-mortem data, did verbal autopsies, and collected post-mortem samples via minimally invasive tissue sampling from stillbirths (weighing at least 1000 g or with an estimated gestational age of at least 28 weeks) and children who died younger than 5 years. Children-or their mothers, in the case of stillbirths and deaths in children younger than 6 months-had to have lived in the catchment area for the past 6 months to be included. Molecular, microbiological, and histopathological analyses were done in collected samples. Cause of death was established by an expert panel on the basis of these data and classified as underlying, comorbid, or immediate separately for stillbirths, neonatal deaths (deaths aged 0-27 days), and child deaths (aged 28 days to <5 years). Findings Between Feb 4, 2019, and Feb 3, 2021, 312 deaths were eligible for inclusion, and the families gave consent in 195 (63%) cases. Cause of death was established in 193 (99%) cases. Among 114 stillbirths, the underlying cause of death was perinatal asphyxia or hypoxia in 60 (53%) and birth defects in 24 (21%). Among 59 neonatal deaths, the most common underlying cause was perinatal asphyxia or hypoxia (17 [29%]) and the most common immediate cause of death was neonatal sepsis, which occurred in 27 (60%). Among 20 deaths in children aged 28 days to 59 months, malnutrition was the leading underlying cause (15 [75%]) and infections were common immediate and comorbid causes. Pathogens were identified in 19 (95%) child deaths, most commonly Klebsiella pneumoniae and Streptococcus pneumoniae. Interpretation Perinatal asphyxia or hypoxia, infections, and birth defects accounted for most stillbirths and child deaths. Most deaths could have been prevented with feasible interventions, such as improved maternity services, folate supplementation, and improved vaccine uptake.

Even though the COVID-19 vaccine has been available and free of charge to the targeted population in Ethiopia, the vaccination rate was lower than needed to achieve herd immunity at community level. This study aimed to explore community perceptions of COVID-19 and vaccine hesitancy in selected cities of Ethiopia involving 70 in-depth interviews and 28 focused group discussions. The audio-taped data were transcribed verbatim, translated into English, and analyzed using a qualitative content analysis approach using the ATLAS.ti software version 8. The findings revealed that COVID-19 was perceived as evil and caused fear and frustration upon its emergence. The community initially used traditional remedies for its prevention but later transitioned to employing non-pharmaceutical interventions. The primary reasons for vaccine hesitancy were misinformation and misconceptions, such as connecting the vaccine with the mark of the beast, a lack of trust due to the multiple vaccine types, a shorter production timeline resulting in distrust of its effectiveness, and a fear of pain and side effects. Based on our findings, we recommend monitoring the use of social media and countering misinformation with the correct information and continuous public health campaigns. Further studies should be conducted to assess the types and magnitude of impacts from the myths and misconceptions on vaccination uptake.

BackgroundInterferon-γ (IFN-γ) is a key cytokine inducing protective immune responses during tuberculosis (TB) infection. Helminth-induced immune responses may affect IFN-γ production by T cells, although its connection with disease severity and immune recovery during treatment is unexplored. We investigated the species-specific effect of helminths on the IFN-γ production by T cells in relation to disease severity during active and latent TB infection (LTBI).MethodsIn this study, 69 active pulmonary TB patients (PTB), 28 with LTBI and 66 healthy controls were included. Active TB was diagnosed using GenXpert MTB/RIF while QuantiFERON test (QFT) was used for the screening of healthy community controls (CCs) and for the diagnosis of LTBI. Helminth infection was identified by routine diagnosis whereas clinical disease severity was evaluated by the TB score. Intracellular IFN-γ production of T cells in stimulated peripheral blood mononuclear cells (PBMCs) was analyzed by flow cytometry using TB antigens (PPD), the polyclonal T cell activator staphylococcal enterotoxin B (SEB), or medium as unstimulated control.ResultsHelminth infected CCs and LTBI subjects showed a significant reduction of IFN-γ+ CD4+ T cells by PPD-stimulation compared to non-helminth infected control groups. The significant reduction in the frequency of IFN-γ+ T cells in both latent and active PTB patients following SEB stimulation was mostly attributed to Schistosoma mansoni infection, whereas Ascaris lumbricoides, Schistosoma mansoni, and hookworm infection contributed equally in CCs. Following anti-helminthic and anti-TB treatment for 2 months, the frequency of IFN-γ+ CD4 T cells in helminth coinfected PTB was restored to levels of helminth negative PTB before treatment. Helminth coinfected PTB patients with an intermediate and severe clinical course had reduced capacity for production of IFN-γ+ T cells compared to the corresponding non-helminth infected PTB.ConclusionWe found a reduction in IFN-γ producing T cells by helminth coinfection which was restored following anti-helminthic treatment. This reduction was helminth species-dependent in an exploratory sub-analysis and correlated to increased disease severity.