Endemic Settings Research Articles

Sero-prevalence and risk factors associated with occurrence of anti-Brucella antibodies among slaughterhouse workers in Uganda.

Brucellosis is a febrile zoonosis occurring among high-risk groups such as livestock keepers and abattoir workers and is a public health priority in Uganda. The technical complexities of bacteriological and molecular methods make serological approaches the cornerstone of diagnosis of human brucellosis in resource limited settings. Therefore, proper application and interpretation of serological tests is central to achieve a correct diagnosis. We conducted a cross-sectional study to estimate the seroprevalence and factors associated with anti-Brucella antibodies among slaughterhouse workers processing ruminants and pigs in three regions of the country with serial testing using a combination of the Rose Bengal Test (RBT) and the BrucellaCapt test. An authorized clinician collected 543 blood samples from consenting abattoir workers as well as attribute medical and social demographic data. Univariable and multivariable logistic regression were used to determine factors associated with anti-Brucella sero-positivity. The sero-prevalence among ruminant slaughterhouse workers ranged from 7.3% (95% CI: 4.8-10.7) using BrucellaCapt to 9.0% (95% CI: 6.3-12.7) using RBT. Slaughterhouse workers from the Eastern regions (AOR = 9.84, 95%CI 2.27-69.2, p = 0.006) and those who graze animals for alternative income (AOR = 2.36, 95% CI: 1.91-6.63, p = 0.040) were at a higher risk of exposure to Brucella. Similarly, those who wore Personal Protective Equipment (AOR = 4.83, 95%CI:1.63-18.0, p = 0.009) and those who slaughter cattle (AOR = 2.12, 95%CI: 1.25-6.0, p = 0.006) were at a higher risk of exposure to Brucella. Those who slaughter small ruminants (AOR = 1.54, 95%CI: 1.32-4.01, p = 0.048) were also at a higher risk of exposure to Brucella. Our study demonstrates the combined practical application of the RBT and BrucellaCapt in the diagnosis of human brucellosis in endemic settings. Both pharmaceutical (e.g., routine testing and timely therapeutic intervention), and non-pharmaceutical (e.g., higher index of suspicion of brucellosis when investigating fevers of unknown origin and observation of strict abattoir hygiene) countermeasures should be considered for control of the disease in high-risk groups.

The integration of Coxiella burnetii PCR testing in serum into the diagnostic algorithm of suspected acute Q fever in an endemic setting.

Our study suggests in a diagnostic stewardship approach the integration of molecular testing (Coxiella burnetii targeted PCR) for the diagnosis of acute Q fever in a reliable time in the endemic setting. Integrating PCR detecting Coxiella burnetii in serum in routine testing of suspected early acute Q fever based on serology result increased the PCR positivity rate significantly. Adding increased transaminases optimizes PCR utility which is highly requested particularly in endemic areas.

Efficacy of typhoid vaccines against culture-confirmed Salmonella Typhi in typhoid endemic countries: a systematic review and meta-analysis

Typhoid is a serious public health threat in many low-income and middle-income countries. Several vaccines for typhoid have been recommended by WHO for typhoid prevention in endemic countries. This study aimed to review the efficacy of typhoid vaccines against culture-confirmed Salmonella enterica serovar Typhi. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for studies published in English between Jan 1, 1986 and Nov 2, 2023. We included randomised controlled trials (RCTs) comparing typhoid vaccines with a placebo or another vaccine. This meta-analysis evaluated the efficacy and safety of several typhoid vaccines, including live attenuated oral Ty21a vaccine, Vi capsular polysaccharide (Vi-PS), Vi polysaccharide conjugated to recombinant Pseudomonas aeruginosa exotoxin A vaccine (Vi-rEPA), and Vi-tetanus toxoid conjugate vaccine (TCV). The certainty of evidence for key outcomes was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations methodology. The outcome of interest was typhoid fever confirmed by the isolation of Salmonella enterica serovar Typhi in blood and adverse events following immunisation. This study is registered with PROSPERO (CRD42021241043). We included 14 RCTs assessing four different vaccines (Ty21a: four trials; Vi-PS: five trials; Vi-rEPA: one trial; TCV: four trials) involving 585 253 participants. All trials were conducted in typhoid endemic countries and the age of participants ranged from 6 months to 50 years. The pooled efficacy against typhoid fever was 45% (95% CI 33-55%; four trials; 247 649 participants; I2 59%; moderate certainty) for Ty21a and 58% (44-69%; five trials; 214 456 participants; I2 34%; moderate certainty) for polysaccharide Vi-PS. The cumulative efficacy of two doses of Vi-rEPA vaccine at 2 years was 91% (88-96%; one trial; 12 008 participants; moderate certainty). The pooled efficacy of a single shot of TCV at 2 years post-immunisation was 83% (77-87%; four trials; 111 130 participants; I2 0%; moderate certainty). All vaccines were safe, with no serious adverse effects reported in the trials. The existing data from included trials provide promising results regarding the efficacy and safety of the four recommended typhoid vaccines. TCV and Vi-rEPA were found to have the highest efficacy at 2 years post-immunisation. However, follow-up data for Vi-rEPA are scarce and only TCV is pre-qualified by WHO. Therefore, roll-out of TCV into routine immunisation programmes in typhoid endemic settings is highly recommended. There was no funding source for this study.

Outcomes of rheumatic fever in Uganda: a prospective cohort study

Rheumatic heart disease is the largest contributor to cardiac-related mortality in children worldwide. Outcomes in endemic settings after its antecedent illness, acute rheumatic fever, are not well understood. We aimed to describe 3-5 year mortality, acute rheumatic fever recurrence, changes in carditis, and correlates of mortality after acute rheumatic fever. We conducted a prospective cohort study of Ugandan patients aged 4-23 years who were diagnosed with definite acute rheumatic fever using the modified 2015 Jones criteria from July 1, 2017, to March 31, 2020, enrolled at three rheumatic heart disease registry sites in Uganda (in Mbarara, Mulago, or Lira), and followed up for at least 1 year after diagnosis. Patients with congenital heart disease were excluded. Patients underwent annual review, most recently in August, 2022. We calculated rates of mortality and acute rheumatic fever recurrence, tabulated changes in carditis, performed Kaplan-Meier survival analyses, and used Cox regression models to identify correlates of mortality. Data were collected between Sept 1 and Sept 30, 2022. Of 182 patients diagnosed with definite acute rheumatic fever, 156 patients were included in the analysis. Of these 156 patients (77 [49%] male and 79 (51%) female; data on ethnicity not collected), 25 (16%) died, 21 (13%) had a cardiac-related death, and 17 (11%) had recurrent acute rheumatic fever over a median of 4·3 (IQR 3·0-4·8) years. 16 (24%) of the 25 deaths occurred within 1 year. Among 131 (84%) of 156 survivors, one had carditis progression by echo. Moderate-to-severe carditis (hazard ratio 12·7 [95% CI 3·9-40·9]) and prolonged PR interval (hazard ratio 4·4 [95% CI 1·7-11·2]) at acute rheumatic fever diagnosis were associated with increased cardiac-related mortality. These are the first contemporary data from sub-Saharan Africa on medium-term acute rheumatic fever outcomes. Mortality rates exceeded those reported elsewhere. Most decedents already had chronic carditis at initial acute rheumatic fever diagnosis, suggesting previous undiagnosed episodes that had already compounded into rheumatic heart disease. Our data highlight the large burden of undetected acute rheumatic fever in these settings and the need for improved awareness of and diagnostics for acute rheumatic fever to allow earlier detection. Strauss Award at Cincinnati Children's Hospital, American Heart Association, and Wellcome Trust.

Systems and computational analysis of gene expression datasets reveals GRB-2 suppression as an acute immunomodulatory response against enteric infections in endemic settings.

Enteric infections are a major cause of under-5 (age) mortality in low/middle-income countries. Although vaccines against these infections have already been licensed, unwavering efforts are required to boost suboptimalefficacy and effectiveness in regions that are highly endemic to enteric pathogens. The role of baseline immunological profiles in influencing vaccine-induced immune responses is increasingly becoming clearer for several vaccines. Hence, for the development of advanced and region-specific enteric vaccines, insights into differences in immune responses to perturbations in endemic and non-endemic settings become crucial. For this reason, we employed a two-tiered system and computational pipeline (i) to study the variations in differentially expressed genes (DEGs) associated with immune responses to enteric infections in endemic and non-endemic study groups, and (ii) to derive features (genes) of importance that keenly distinguish between these two groups using unsupervised machine learning algorithms on an aggregated gene expression dataset. The derived genes were further curated using topological analysis of the constructed STRING networks. The findings from these two tiers are validated using multilayer perceptron classifier and were further explored using correlation and regression analysis for the retrieval of associated gene regulatory modules. Our analysis reveals aggressive suppression of GRB-2, an adaptor molecule integral for TCR signaling, as a primary immunomodulatory response against S. typhi infection in endemic settings. Moreover, using retrieved correlation modules and multivariant regression models, we found a positive association between regulators of activated T cells and mediators of Hedgehog signaling in the endemic population, which indicates the initiation of an effector (involving differentiation and homing) rather than an inductive response upon infection. On further exploration, we found STAT3 to be instrumental in designating T-cell functions upon early responses to enteric infections in endemic settings. Overall, through a systems and computational biology approach, we characterized distinct molecular players involved in immune responses to enteric infections in endemic settings in the process, contributing to the mounting evidence of endemicity being a major determiner of pathogen/vaccine-induced immune responses. The gained insights will have important implications in the design and development of region/endemicity-specific vaccines.

Seroprevalence of hepatitis B virus infection (HBsAg) and associated factors among antenatal clinic attendees in a secondary-level facility in southern Ghana

IntroductionVertical transmission of Hepatitis B Virus (HBV) infection is the predominant mode of HBV transmission in highly endemic settings worldwide where the HBV seroprevalence is above 8%. Newborns who contract HBV at birth have a higher risk of chronic infections that can result in liver cancer and liver cirrhosis. Preventing mother-to-child transmission of HBV through screening of pregnant women during the antenatal period and universal vaccination of newborns are important strategies for eliminating new childhood HBV infections. This study sought to estimate the prevalence of HBV infection among pregnant women in the study area and to determine the factors associated with a positive HBV disease status. The findings from this study will help in obtaining a baseline for comparing future trends and identifying risk factors for HBV that need to be eliminated in southern Ghana. MethodsThis was a cross-sectional hospital-based analytic study in which 225 pregnant women were surveyed using a semi structured questionnaire. Blood samples were taken and analysed qualitatively for HBsAg. The data were entered into Epi-data version 3.1 and exported into STATA version 17 for analysis, with a significance level set at <0.05. ResultsThis study revealed that the seroprevalence of HBV infection (HBsAg positivity) was 8.0% CI (5%–12.4%) among the pregnant women. The HBV vaccination coverage was 50.2%. Pregnant women with a history of sexually transmitted diseases were six times more likely to test positive for HBsAg aOR: 6.36 (CI = 0.35–2.92, p = 0.019). Additionally, women who had received at least one dose of the HBV vaccine had lower odds of having HBV infection than did those who failed to vaccinate (aOR = 0.08, 95% CI = 0.01–0.66, P = 0.020). ConclusionsThe prevalence of HBV infection is relatively high in this population. HBV vaccination and sexually transmitted infections play significant roles in HBV infection and transmission in the study area. Interventions to promote HBV vaccination among the adult population as well as among newborns and STI prevention strategies are needed to reverse the trend of HBV infections in the study area.

“So that’s why I found PrEP to be safest way to protect yourself”: exploring IPV experiences and impact on HIV prevention among pregnant and postpartum women in Cape Town, South Africa

Intimate partner violence (IPV) occurs at alarmingly high rates towards pregnant women in South Africa. Experiences of emotional, physical, and sexual IPV in pregnancy can adversely impact the health and safety of mother and fetus. Furthermore, IPV is associated with increased risk of HIV, exacerbating the public health impact of violence among pregnant women in this HIV endemic setting. In-depth understanding of cultural and contextual drivers of experiences of IPV is a critical precursor to development of interventions effectively addressing this issue among pregnant women in South Africa. The present study examines factors contributing to IPV among pregnant women to identify potential points of intervention. We conducted twenty in-depth interviews with postpartum women who used oral pre-exposure prophylaxis (PrEP) in pregnancy and reported recent experiences of IPV and/or ongoing alcohol use in a township near Cape Town, South Africa that experiences a heavy burden of both HIV and IPV. Interpretive thematic analysis was used. Several patterns of IPV during pregnancy were identified and violence was frequently described as co-occurring with male partner alcohol use. A majority of women referenced oral PrEP as their preferred method for HIV prevention, highlighting the agency and discretion it provided as beneficial attributes for women experiencing IPV. Fear of judgement from peers for remaining with an abusive partner and a lack of clear community messaging around IPV were identified as barriers to disclosure and support-seeking. Addressing the lack of social support received by women experiencing IPV during pregnancy in South Africa is essential to comprehensive IPV programming.

Comprehensive Genomic Analysis Identifies a Diverse Landscape of Sideroblastic and Nonsideroblastic Iron-Related Anemias with Novel and Pathogenic Variants in an Iron-Deficient Endemic Setting

Inherited iron metabolism defects are possibly missed or underdiagnosed in iron-deficient endemic settings due to a lack of awareness or a methodical screening approach. Hence, we planned a systematic evaluation of anemia cases (2019-2021) based on clinical phenotype, normal screening tests (HPLC, alpha gene sequencing, ESR, CRP, tTG), and abnormal iron profile by targeted NGS (26 gene-panel) supplemented with whole exome, MLPA/mtDNA sequencing and CMA. Novel variants in ALAS2, STEAP3, and HSPA9 genes were functionally validated. 290 anemia cases were screened and 41 (14%) enrolled for genomic testing as per inclusion criteria. Comprehensive genomic testing revealed pathogenic variants in 23/41 (56%) cases. Congenital sideroblastic anemia (CSA) was the most common diagnosis (14/23;61%) with pathogenic variations in ALAS2 (6), SLC25A38 (3), HSPA9 (2) and HSCB, SLC19A2 and mtDNA deletion (1 each). Non-sideroblastic iron defects included STEAP3-related microcytic anemia (2/23;8.7%) and hypotransferrenemia (1/23;4.3%). 6/22 (27%) revealed a non-iron metabolism gene defect on whole exome sequencing. A total of 11 novel variants (including VUS) were noted in 13 cases. Genotype-phenotype correlation revealed a significant association of frameshift/nonsense/splice variants with lower presentation age (0.8 months vs. 9 years; p-<0.01) compared to missense variants. The systematic evaluation helped uncover an inherited iron defect in 41% (17/41) cases, suggesting the need for active screening and awareness for these rare diseases in an iron deficient endemic population.

Agreement between Handheld and Standard Echocardiography for Diagnosis of Latent Rheumatic Heart Disease in Brazilian Schoolchildren from High-Prevalence Settings (Agreement between Screening and Standard Echo for RHD).

Introduction: Handheld echocardiography (echo) is the tool of choice for rheumatic heart disease (RHD) screening. We aimed to assess the agreement between screening and standard echo for latent RHD diagnosis in schoolchildren from an endemic setting. Methods: Over 14 months, 3 nonphysicians used handheld machines and the 2012 WHF Criteria to determine RHD prevalence in consented schoolchildren from Brazilian low-income public schools. Studies were interpreted by telemedicine by 3 experts (Brazil, US). RHD-positive children (borderline/definite) and those with congenital heart disease (CHD) were referred for standard echo, acquired and interpreted by a cardiologist. Agreement between screening and standard echo, by WHF subgroups, was assessed. Results: 1390 students were screened in 6 schools, with 110 (7.9%, 95% CI 6.5-9.5) being screen positive (14 ± 2 years, 72% women). Among 16 cases initially diagnosed as definite RHD, 11 (69%) were confirmed, 4 (25%) reclassified to borderline, and 1 to normal. Among 79 cases flagged as borderline RHD, 19 (24%) were confirmed, 50 (63%) reclassified to normal, 8 (10%) reclassified as definite RHD, and 2 had mild CHD. Considering the 4 diagnostic categories, kappa was 0.18. In patients with borderline RHD reclassified to non-RHD, the most frequent WHF criterion was B (isolated mitral regurgitation, 64%), followed by A (2 mitral valve morphological features, 31%). In 1 patient with definite RHD reclassified to normal, the WHF criterion was D (borderline RHD in aortic and mitral valves). After standard echo, RHD prevalence was 3.2% (95% CI 2.3-4.2). Conclusions: Although practical, RHD screening with handheld devices tends to overestimate prevalence.

Chikungunya seroprevalence, force of infection, and prevalence of chronic disability after infection in endemic and epidemic settings: a systematic review, meta-analysis, and modelling study

Chikungunya is an arboviral disease transmitted by Aedes aegypti and Aedes albopictus mosquitoes with a growing global burden linked to climate change and globalisation. We aimed to estimate chikungunya seroprevalence, force of infection (FOI), and prevalence of related chronic disability and hospital admissions in endemic and epidemic settings. In this systematic review, meta-analysis, and modelling study, we searched PubMed, Ovid, and Web of Science for articles published from database inception until Sept 26, 2022, for prospective and retrospective cross-sectional studies that addressed serological chikungunya virus infection in any geographical region, age group, and population subgroup and for longitudinal prospective and retrospective cohort studies with data on chronic chikungunya or hospital admissions in people with chikungunya. We did a systematic review of studies on chikungunya seroprevalence and fitted catalytic models to each survey to estimate location-specific FOI (ie, the rate at which susceptible individuals acquire chikungunya infection). We performed a meta-analysis to estimate the proportion of symptomatic patients with laboratory-confirmed chikungunya who had chronic chikungunya or were admitted to hospital following infection. We used a random-effects model to assess the relationship between chronic sequelae and follow-up length using linear regression. The systematic review protocol is registered online on PROSPERO, CRD42022363102. We identified 60 studies with data on seroprevalence and chronic chikungunya symptoms done across 76 locations in 38 countries, and classified 17 (22%) of 76 locations as endemic settings and 59 (78%) as epidemic settings. The global long-term median annual FOI was 0·007 (95% uncertainty interval [UI] 0·003-0·010) and varied from 0·0001 (0·00004-0·0002) to 0·113 (0·07-0·20). The highest estimated median seroprevalence at age 10 years was in south Asia (8·0% [95% UI 6·5-9·6]), followed by Latin America and the Caribbean (7·8% [4·9-14·6]), whereas median seroprevalence was lowest in the Middle East (1·0% [0·5-1·9]). We estimated that 51% (95% CI 45-58) of people with laboratory-confirmed symptomatic chikungunya had chronic disability after infection and 4% (3-5) were admitted to hospital following infection. We inferred subnational heterogeneity in long-term average annual FOI and transmission dynamics and identified both endemic and epidemic settings across different countries. Brazil, Ethiopia, Malaysia, and India included both endemic and epidemic settings. Long-term average annual FOI was higher in epidemic settings than endemic settings. However, long-term cumulative incidence of chikungunya can be similar between large outbreaks in epidemic settings with a high FOI and endemic settings with a relatively low FOI. International Vaccine Institute.

Modelling spatiotemporal patterns of visceral leishmaniasis incidence in two endemic states in India using environment, bioclimatic and demographic data, 2013-2022.

As of 2021, the National Kala-azar Elimination Programme (NKAEP) in India has achieved visceral leishmaniasis (VL) elimination (<1 case / 10,000 population/year per block) in 625 of the 633 endemic blocks (subdistricts) in four states. The programme needs to sustain this achievement and target interventions in the remaining blocks to achieve the WHO 2030 target of VL elimination as a public health problem. An effective tool to analyse programme data and predict/ forecast the spatial and temporal trends of VL incidence, elimination threshold, and risk of resurgence will be of use to the programme management at this juncture. We employed spatiotemporal models incorporating environment, climatic and demographic factors as covariates to describe monthly VL cases for 8-years (2013-2020) in 491 and 27 endemic and non-endemic blocks of Bihar and Jharkhand states. We fitted 37 models of spatial, temporal, and spatiotemporal interaction random effects with covariates to monthly VL cases for 6-years (2013-2018, training data) using Bayesian inference via Integrated Nested Laplace Approximation (INLA) approach. The best-fitting model was selected based on deviance information criterion (DIC) and Watanabe-Akaike Information Criterion (WAIC) and was validated with monthly cases for 2019-2020 (test data). The model could describe observed spatial and temporal patterns of VL incidence in the two states having widely differing incidence trajectories, with >93% and 99% coverage probability (proportion of observations falling inside 95% Bayesian credible interval for the predicted number of VL cases per month) during the training and testing periods. PIT (probability integral transform) histograms confirmed consistency between prediction and observation for the test period. Forecasting for 2021-2023 showed that the annual VL incidence is likely to exceed elimination threshold in 16-18 blocks in 4 districts of Jharkhand and 33-38 blocks in 10 districts of Bihar. The risk of VL in non-endemic neighbouring blocks of both Bihar and Jharkhand are less than 0.5 during the training and test periods, and for 2021-2023, the probability that the risk greater than 1 is negligible (P<0.1). Fitted model showed that VL occurrence was positively associated with mean temperature, minimum temperature, enhanced vegetation index, precipitation, and isothermality, and negatively with maximum temperature, land surface temperature, soil moisture and population density. The spatiotemporal model incorporating environmental, bioclimatic, and demographic factors demonstrated that the KAMIS database of the national programmme can be used for block level predictions of long-term spatial and temporal trends in VL incidence and risk of outbreak / resurgence in endemic and non-endemic settings. The database integrated with the modelling framework and a dashboard facility can facilitate such analysis and predictions. This could aid the programme to monitor progress of VL elimination at least one-year ahead, assess risk of resurgence or outbreak in post-elimination settings, and implement timely and targeted interventions or preventive measures so that the NKAEP meet the target of achieving elimination by 2030.

Success in managing a giant hepatic hydatid cyst: a case report of successful conservative surgical intervention in an endemic setting

Introduction and importance: Echinococcosis, also known as a hydatid cyst, arises from a parasitic infection caused by the larval form of the tapeworm Echinococcus granulosus in humans. This endemic disease in Tunisia presents a significant public health challenge. The case highlights the enormous size of the liver hydatid cyst, emphasizing the importance and success of conservative surgical treatment. Case Presentation: A 45-year-old female shepherdess presented with abdominal pain and a mass, diagnosed as a giant hepatic hydatid cyst. A computed tomography scan revealed a dysmorphic liver with a large multivesicular cyst. Surgical intervention included the resection and closure of multiple cystic fistulas. Postoperative recovery was uneventful and at the 6-month follow-up, the patient displayed no indications of recurrence. Clinical discussion: Echinococcosis, prevalent in livestock-farming regions, primarily affects the liver and lungs. It often remains asymptomatic, detected incidentally. Diagnosis relies on imaging, with surgical excision as the primary treatment. Percutaneous options exist but are less effective. Serologies are underused. Management challenges include complications and recurrence. Conservative surgery is common but faces complications. Radical surgery is more effective, albeit complex. Albendazole preoperatively proves promising, reducing cyst viability. Regular follow-up is crucial for recurrence detection. Conclusion: Managing giant hepatic hydatid cysts requires tailored approaches, especially in endemic regions. Our success with conservative surgical treatment highlights its effectiveness in confronting formidable cyst sizes, informing clinical practice, and contributing to the medical literature.

P769 Impact of discontinuation of anti-TNF therapy: A long term follow-up data of risks and predictors relapse in a large Indian cohort

Abstract Background Discontinuation of anti-TNF therapy in IBD is an important consideration in TB endemic low resource settings of the developing world. There are no established guidelines on withdrawal of biologics. A proper exit strategy on when and how biologics can be stopped is therefore warranted. We aimed to identify risk factors and rates of relapse post withdrawal in a large real-life cohort of patients from India. Methods Prospectively collected data of consecutive patients treated with anti-TNFs from the IBD registry of a large tertiary care centre was analyzed. Demographics,baseline disease characteristics,reasons for discontinuation, response to anti-TNF,and relapse rate after withdrawal were analysed. Time to event analysis was done to evaluate relapse rates over time. Cox proportional hazard analysis and non-parametric tests were performed to identify risk factors of relapse. Results Of 8300 patients, only 725(8.7%),(Median age-36y,IQR:26-47,61.2% male,61.2%CD, 32%UC, IBD-U 1.8%) received anti-TNFs. 445 (61.3%) discontinued with median follow up of 54 m(IQR:31-81). Reasons for discontinuation were primary non-response(64,14.3%);secondary loss of response (44,9.8%);financial constraints(27,6.1%);TB reactivation (18,4%), side effects(17,3.2%); infusion reactions(20,4.4%);non-compliance(4,0.9%), and COVID lockdown (6,1.3%). Overall, 232/445 (52%) were in clinical and endoscopic remission while stopping anti-TNFs with median follow up of 41 months(IQR:24.5-67). Relapse rates at 1,2,3,4, and 5 years after discontinuation were 16%,5.6%,5.2%,2.6% and 1.3% respectively. Overall,161/232(69%) patients remained in remission(Fig1A). Patients who stopped after clinical and endoscopic remission had higher likelihood of maintaining remission after discontinuation of biologics (Log-rank test,p=0.001). On multivariate analysis, fistulizing disease(p=0.03), prior history of bowel surgery (p=0.019), immunomodulator usage (p=0.001) and shorter duration of therapy (p=0.017) were associated with significantly higher rate of relapse(Table1). Cumulative time to relapse was significantly longer in those with or without endoscopic remission (median 17.3 vs 7 months;p=0.04)(Fig1B). On the other hand, shorter disease duration (p=0.001) and absence of extra-intestinal manifestations (p=0.009) were associated with lower risks of relapse. Conclusion 60% of patients discontinued anti-TNF therapy in this real world cohort. However, long-term cumulative relapse rates were low(30%), particularly in non-fistulizing disease, with no history of bowel surgery or extra intestinal manifestations and in endoscopic remission. A definite exit strategy appears feasible and would be a practical and affordable management approach.

Effectiveness of one dose of killed oral cholera vaccine in an endemic community in the Democratic Republic of the Congo: a matched case-control study

A global shortage of cholera vaccines has increased the use of single-dose regimens, rather than the standard two-dose regimen. There is sparse evidence on single-dose protection, particularly in children. In 2020, a mass vaccination campaign was conducted in Uvira, an endemic urban setting in eastern Democratic Republic of the Congo, resulting in largely single-dose coverage. We examined the effectiveness of a single-dose of the oral cholera vaccine Euvichol-Plus in this high-burden setting. In this matched case-control study, we recruited individuals with medically attended confirmed cholera in the two cholera treatment facilities in the city of Uvira. The control group consisted of age-matched, sex-matched, and neighbourhood-matched community individuals. We recruited across two distinct periods: Oct 14, 2021, to March 10, 2022 (12-17 months after vaccination), and Nov 21, 2022, to Oct 18, 2023 (24-36 months after vaccination). Study staff administered structured questionnaires to all participants to capture demographics, household conditions, potential confounding variables, and vaccination status. The odds of vaccination for the case and control groups were contrasted in conditional logistic regression models to estimate unadjusted and adjusted vaccine effectiveness. We enrolled 658 individuals with confirmed cholera and 2274 matched individuals for the control group. 99 (15·1%) individuals in the case group were younger than 5 years at the time of vaccination. The adjusted single-dose vaccine effectiveness was 52·7% (95% CI 31·4 to 67·4) 12-17 months after vaccination and 44·7% (24·8 to 59·4) 24-36 months after vaccination. Although protection in the first 12-17 months after vaccination was similar for children aged 1-4 years and older individuals, the estimate of protection in children aged 1-4 years appeared to wane during the third year after vaccination (adjusted vaccine effectiveness 32·9%, 95% CI -30·7 to 65·5), with CIs spanning the null. A single dose of Euvichol-Plus provided substantial protection against medically attended cholera for at least 36 months after vaccination in this cholera-endemic setting. Although the evidence provides support for similar levels of protection in young children and others in the short term, protection among children younger than 5 years might wane significantly during the third year after vaccination. Wellcome Trust and Gavi, the Vaccine Alliance.

Fecal Shedding, Antimicrobial Resistance and In Vitro Biofilm formation on Simulated Gallstones by Salmonella Typhi Isolated from Typhoid Cases and Asymptomatic Carriers in Nairobi, Kenya.

Typhoid fever, caused by the human restricted pathogen Salmonella Typhi, remains a major global public health concern. Even after successful treatment, approximately 3-5% of patients with typhoid fail to clear the bacteria within one year and become chronic carriers. Most typhoid carriers have gallstones in their gallbladder, and biofilm formation on gallstones is highly correlated with chronic carriage. This study's goal was to identify asymptomatic typhoid carriers in an endemic setting in Kenya, and to compare acute versus chronic isolates. A cohort of typhoid fever patients identified through blood and/or stool culture, and their household contacts, were followed up after treatment to detect longitudinal S. Typhi stool shedding. An abdominal ultrasound scan was used to identify individuals with gallstones. A total of 32 index patients and 32 household contacts were successfully followed-up. Gallstones were detected in 4 cases and 1 household contact. The duration of S. Typhi shedding was significantly longer in individuals with gallstones compared to those without, P<0.001. Eighty-three (83) S. Typhi strains were tested for susceptibility to commonly used antimicrobials and examined by in vitro biofilm formation assays. Out of 37 infected individuals, 32.4% had infections caused by multidrug resistant (MDR) S. Typhi strains and only 18.9% were infected by susceptible strains. Non-MDR strains formed significantly better biofilms in vitro than the MDR strains (P<0.001). This study provides data on S. Typhi chronic carriage that will influence public health approaches aimed at reducing typhoid transmission and the burden of infection.

Genotypic Diversity among Salmonella Typhi Isolated from Children Living in Informal Settlements in Nairobi, Kenya.

The persistence of multidrug-resistant (MDR) Salmonella Typhi (S. Typhi) is a challenge especially in regions where typhoid is endemic. Surveillance of circulating genotypes of MDR S. Typhi is crucial in typhoid acute cases and carriers. This study aimed to investigate genotypic diversity of S. Typhi from symptomatic and asymptomatic children in endemic settings in Nairobi, Kenya. Symptomatic and asymptomatic individuals' ≤ 16 years were recruited at four health facilities and tested for typhoid through stool cultures. The S. Typhi isolates were subjected to antibiotic susceptibility testing to investigate multidrug resistance. The MDR S. Typhi isolates' DNA was extracted and illumina sequenced. Raw reads were de novo assembled and analyzed by pathogen-watch. From the 90 sequenced isolates, 60 (67%) were confirmed to be S. Typhi (sequence Type 1 and genotype 4.3.1). Out of the 60 S. Typhi strains; 39 (65%) had plasmids, from these 38 (97%) had IncHI1 plasmids alone. Out of the 60, 59 (98%) S. Typhi isolates had bla TEM-1D . Point mutations conferring reduced susceptibility to quinolones were detected in 42 (70%) of S. Typhi isolates, from these; 14 (33%) had gyrA S83Y, and 28 (67%) gyrB S464F genes, respectively. This study reports 4.3.1 (H58) as the most dominant S. Typhi genotype responsible for spread of MDR phenotypes carried on IncHI1 plasmids. Presence of MDR S. Typhi with resistance genes such as bla TEM-1D and reduced susceptibility to ciprofloxacin especially among asymptomatic individuals, reiterates the need for use of typhoid conjugate vaccine among vulnerable children as a control and prevention measure against typhoid.

Intestinal Helminth Infections and Their Association with QuantiFERON-TB Gold Plus Test Performance in an Endemic Setting, Northwest Ethiopia.

Timely detection and treatment of latent TB infection (LTBI) is part of WHO's strategy against tuberculosis (TB). Helminth infections can modulate immune responses, potentially impacting the performance of interferon-gamma release assays (IGRAs) such as the QuantiFERON-TB Gold Plus (QFT-Plus). This study evaluated the association between helminth infections and QFT-Plus results among participants from a TB-endemic region. A cross-sectional study was conducted from October 2022 to March 2023 in Bahir Dar, Ethiopia. Stool samples of 314 potential participants were examined for helminths using wet mount and Kato-Katz techniques. LTBI was assessed by QFT-Plus from a total of 100 gender-matched helminth-positive and -negative participants. The association between helminth infection status, egg count, and QFT-Plus positivity was analyzed, and p values <0.05 were considered significant. Overall, 53 of 314 screened participants were infected with helminths (16.9%), with A. lumbricoides (47.2%) and hookworm (30.2%) as most prevalent species. The overall QFT-Plus positivity rate was 30.0%, with similar rates observed between helminth-positive and helminth-negative participants. Although QFT-Plus positivity was slightly lower in hookworm carriers (25%) compared to those with A. lumbricoides (32%), a higher-than-median hookworm egg burden was significantly associated with reduced QFT-Plus positivity (P = 0.029). QFT-Plus positivity was significantly higher among male participants than females (P = 0.032). While overall helminth infection status did not significantly affect QFT-Plus positivity, higher hookworm burden was associated with reduced QFT-Plus reactivity. These findings suggest that the type of helminth and infection intensity, rather than its mere presence, may influence IGRA performance. Further studies with larger sample sizes are warranted to understand the species-specific effect of helminth infection on immune modulation of the host.

Praziquantel-related visual disorders among recipients in mass drug administration campaigns in schistosomiasis endemic settings: Systematic review and meta-analysis protocol.

Hundreds of millions of doses of Praziquantel (PZQ) have been administered to persons with and without schistosomiasis living in schistosomiasis endemic settings, through the mass drug administration (MDA) strategy which started in the early 2000s. A recent publication suggested high risk of PZQ-related visual disorders, raising public health concerns. We aim to systematically synthesize evidence on the magnitude of PZQ-related visual disorders. We will search PubMed, Google Scholar, CINAHL, SCOPUS, CENTRAL and LILACS from 1977 (when the first human clinical trials on PZQ started) to 31st May 2024, with no language restrictions. The key search terms will include "Praziquantel", "PZQ", "visual disorder", "adverse events", "side effects", "blurry vision" and "visual impairment" together with alternative terms and synonyms. All the countries endemic for schistosomiasis will be included as search terms. We will also search HINARI, Africa Journals Online, Thesis Databases and Preprint Repositories. Where necessary, we will contact expert researchers working in the field of schistosomiasis, UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), pharmaceutical industries, country-specific Food and Drug Authorities (FDAs) and the European Medicines Agency databases. We will search Conference Proceedings and reference lists of relevant studies for additional studies. At least two authors will independently select studies, extract data and assess risk of bias in the included studies. Any disagreements or discrepancies will be resolved through discussion between the reviewers. Heterogeneity will be explored graphically, and statistically using the I2-statistic. We will conduct random-effects meta-analysis when heterogeneity is appreciable, and express dichotomous outcomes (visual adverse events including excessive lacrimation, blurry vision and visual impairments) as risk ratio (RR) or Odds Ratio (OR) with their 95% confidence interval (CI). We will perform subgroup analysis to assess the impact of heterogeneity, and sensitivity analyses to test the robustness of the effect estimates. The overall level of evidence will be assessed using GRADE. The present review expects to identify and categorize visual disorders occurring after administration of PZQ, alone or in combination with other drugs. By synthesizing the data from multiple studies, the review aims to present a quantitative assessment of the risk or odds of experiencing a visual disorder in different populations after ingesting PZQ. The review will also generate insights into whether PZQ in combination with other drugs are associated with increased odds of visual disorders and whether the occurrence of visual disorders correlates with dosage or treatment duration. Policymakers, public health experts and stakeholders could rely on the review findings to deliver context-sensitive preventive chemotherapy programs by adjusting drug combinations or dosing schedules to reduce risk of visual adverse effects in populations treated with PZQ. The review aims to identify gaps in the current evidence regarding visual disorders following PZQ administration in schistosomiasis endemic settings which can serve as the basis for future research on important but unanswered questions. The findings of this study will be disseminated through stakeholder forums, conferences, and peer-review publications. The review protocol has been registered in the International Prospective Register for Systematic Reviews (PROSPERO)- CRD42023417963.

Factors associated with trachoma in persistently endemic setting in Southern Ethiopia: a community-based cross-sectional study.

in Ethiopia, despite implementing decades-long surgery, antibiotics, facial cleanliness, and environmental improvement interventions, commonly known as the SAFE strategies, persistence and recrudescence of trachoma are common. There is limited evidence that explained the reasons. This study assesses factors associated with trachoma in persistently endemic settings. using a World Health Organization (WHO)-endorsed Global Trachoma Mapping Methodology, a two-stage cluster sampling technique was applied to select 1538 study respondents from 52 clusters. Data was collected using ODK and analysed using SPSS 28. A total of 1522 respondents were enrolled. the mean age of the respondents was 33.4 and 50.5% of the respondents were females. About 32.3% (CI 30%, 34%) of the households reported the presence of at least one member of the family having one or more symptoms of trachoma. Being from poorer household (AOR=1.36, 95% CI: 1.0,1.75), presence of a household member who did not receive optimum treatment (AOR=2.8, 95% CI: 1.5, 5.2), and less than 3 doses of treatment (AOR=1.94, 95% CI: 1.32, 2.86) and presence of children ever not treated (AOR= 2.5, 95% CI: 1.5, 4.2) are associated with increased risk of manifesting symptoms of trachoma. In contrast, having optimally treated members of household (AOR=11.2,95% CI: 6.5, 19.3) and face washing with soap (AOR=0.59, 95% CI 36, 0.97) were preventive. trachoma is a persistent problem in the study districts. Generally, persistent, and recrudescent districts are characterised by segments of population missing optimum treatment as well as poor sanitation and hygiene practices. Our evidence supports the importance of adhering to optimal treatment guidelines, leaving no one behind, and the need for adequate treatment coverage.

Do Blood group and Sickle cell trait protect against placental malaria?

Blood group O is reported to confer some degree of protection from severe malaria in endemic setting. This protection is believed to be due to reduced and smaller rosette formation in people of blood group O which can easily be cleared by the host immune system. Also, sickle cell trait (HbAS) is reported to disrupt the adhesion of infected erythrocytes to microvascular endothelial walls, which could protect pregnant women from placental malaria. We determined the association between HbAS and ABO blood group, and placental malaria amongst pregnant women of all parities. The study enrolled 221 pregnant women. Peripheral blood samples were taken for malaria smears, ABO blood grouping and haemoglobin (Hb) electrophoresis. A struc‑ tured questionnaire was used to age, bed net usage, and the number of Sulphadoxine‑pyrimethamine (SP) doses taken by a pregnant woman. Two hundred and twenty‑one (221) pregnant women were enrolled and out of this number, 110 (49.8%) were primiparae and 111 (50.2%) multiparae, with a mean age of 23.7±5.2. Placental malaria (PM) prevalence by PCR detection was 19.4% (43/221). Of those who were malaria positive 58.1% (25/43) were primiparae. Primiparae who are of blood group O were more susceptible to PM [P=0.04, (OR); 2.85, 95% (Cl), 1.12‑9.01]. But sickle cell trait did not reduce the prevalence of PM [P=0.84 (OR); 0.92, 95% (Cl), 0.43‑1.99]. Non‑blood group O primiparae women were protected against placental malaria. This could be why some primiparae women are protected from PM, just like multiparae women.