National Centre for Disease Control (NCDC; previously known as National Institute of Communicable Diseases) is an institute under the Indian Directorate General of Health Services, Ministry of Health and Family Welfare. It was established in July 1963 for research in epidemiology and control of communicable diseases and to reorganize the activities of the Malaria Institute of India (MII). Currently it has eight branches at Alwar, Bengaluru, Trivandrum, Calicut, Coonoor, Jagdalpur, Patna, Rajahmundry and Varanasi to advise the respective state governments on public health. The headquarters are in Sham Nath Marg in New Delhi.
BACKGROUND:Klebsiella pneumoniae causes ~20% of sepsis in neonates, with ~40% crude mortality. A vaccine administered to pregnant women, protecting against ≥70% of K. pneumoniae infections, could avert ~400,000 cases and ~80,000 deaths annually, mostly in Africa and South Asia. Vaccine formulations targeting the capsular polysaccharide (K) or lipopolysaccharide (O) antigens are in development. Global K. pneumoniae populations display extensive K and O diversity, necessitating a polyvalent vaccine targeted to the serotypes associated with neonatal disease in relevant geographical regions. We investigated the prevalence of K and O types associated with neonatal sepsis in Africa and South Asia to inform maternal vaccine design. METHODS AND FINDINGS:We analysed 1,930 K. pneumoniae neonate blood isolates from 13 surveillance studies across 35 sites in 13 countries. We used pathogen whole-genome sequencing to predict K and O serotypes and adjust for local transmission clusters, and Bayesian hierarchical meta-analysis to estimate K and O prevalence overall and per region, treating site as a random effect. Eighty-seven K loci were identified. KL2, KL102, KL25, KL15, and KL62 accounted for 49% of isolates. We estimate that 20 K loci, combining the eight most prevalent per region, could cover 72.9% of all infections (95% credible interval: [69.4%, 76.5%]) and ≥70% in each of Eastern, Western, and Southern Africa and South Asia. Preliminary findings from three sites suggested sufficient temporal stability of K loci to maintain 20-valent K vaccine coverage over 5-10 years, but more longitudinal data are needed to support this prediction. O types were far less diverse (n = 14 types). We estimate the top-5 (O1⍺β,2⍺, O1⍺β,2β, O2⍺, O2β, and O4) would cover 86.2% [82.6, 89.9%] of total infections (76%-92% per region), while the top-10 would cover ~99% of infections in all four regions. The main limitations of our study are the reliance on genome sequences to predict K and O serotypes (as serological typing is not available) and a lack of longitudinal data to explore stability of antigen prevalence over time. CONCLUSIONS:Neonatal sepsis is associated with diverse K and O types, with substantial geographic and temporal variation even after adjusting for localised transmission clusters. Despite this, a single 20-valent K vaccine could theoretically cover ≥70% of infections in all target regions. Locally-targeted vaccines could achieve higher coverage with lower valency, but are less feasible. In principle, very high coverage could be achieved with lower valency O-based vaccines, however, the protective efficacy against disease of antibodies targeting the O antigen remains uncertain. Further research is needed on cross-reactivity, antigen exposure, and stability of antigens over time, to better inform vaccine development.
BACKGROUND:South Africa faces emerging resistance to tuberculosis drugs like bedaquiline. Phenotypic drug-susceptibility testing (DST), the current reference standard for bedaquiline DST, has long turnaround times. Targeted next-generation sequencing (tNGS) offers a comprehensive alternative, potentially delivering faster results. However, these advantages must be weighed against differences in cost and test accuracy. METHODS:We used a decision tree model to evaluate the cost-effectiveness of tNGS against the standard of care (SOC) in South Africa across different levels of tNGS decentralization. Key outcomes included survival rates, time to a correct resistance profile, infectious time, and disability-adjusted life years (DALYs). Sensitivity analyses assessed the impact of drug-resistance prevalence, tNGS sensitivity, and improved DST access on overall cost-effectiveness. RESULTS:tNGS averted 408 DALYs and correctly identified 90.7% of resistance profiles as compared to 87.7% with SOC. Based on model assumptions for South Africa, tNGS had a reduced turnaround time and averted 97 years of infectious time. Centralized tNGS was cost-saving relative to SOC; however, decentralization of tNGS resulted in higher costs per DALY averted ($671-$2454). tNGS performance, relative to the SOC, improved at higher bedaquiline resistance and with increased sensitivity. Any increase in DST access through tNGS would improve cost-effectiveness in decentralized scenarios. CONCLUSIONS:tNGS could be cost-saving (centralized) or cost-effective (decentralized) in South Africa and has the potential to improve patient outcomes by returning a greater number of correct results in a shorter time. This analysis should be replicated across other settings to evaluate the broader feasibility of tNGS for DST.
The 2022 multi-country mpox (formerly monkeypox) outbreak, driven by mpox virus (MPXV) Clade IIb poses renewed threat to global public health. The cessation of smallpox vaccination has created large immunologically naïve cohorts, with uncertain implications for contemporary MPXV susceptibility. To assess whether residual vaccination-derived immunity influences exposure risk, we combine serological and phylodynamic analyses. Using a six-plex Luminex assay, we measure immunoglobulin G (IgG) binding to six MPXV antigens in 176 Nigerian adults comprising of 75 healthcare workers sampled in 2021 and 101 community volunteers sampled in 2023. At baseline, 24/176 (13.6
OBJECTIVES:The spread of ceftriaxone-resistant Neisseria gonorrhoeae is threatening the last option for gonorrhoea treatment, ceftriaxone. Gepotidacin, the first-in-class triazaacenaphthylene bacterial topoisomerase type IIA inhibitor, recently showed non-inferiority compared to ceftriaxone-azithromycin for treatment of uncomplicated urogenital gonorrhoea in a Phase 3 randomized controlled trial. We evaluated the in vitro susceptibility to gepotidacin in clinical gonococcal isolates (n = 2912), including 125 (4.3%) ceftriaxone-resistant isolates, collected 2021-24 in eight WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) countries in three WHO regions. METHODS:Isolates from Cambodia (n = 474), Indonesia (n = 107), Malawi (n = 111), the Philippines (n = 817), South Africa (n = 578), Thailand (n = 249), Uganda (n = 342) and Vietnam (n = 234) were examined. MICs of gepotidacin were determined using agar dilution. Gepotidacin target genes (gyrA and parC) were examined with Illumina sequencing. RESULTS:Gepotidacin showed high in vitro activity, with MICs ranging from <0.016 to 4 mg/L. The modal MIC was 0.5 mg/L, MIC₅₀ 0.5 mg/L and MIC₉₀ 1 mg/L. Minor variations in the MIC distributions across countries were observed. ParC D86N, which in suboptimal gepotidacin concentrations predisposes for resistance development, was found in 35.5% of isolates. CONCLUSIONS:We show that the in vitro susceptibility to gepotidacin in N. gonorrhoeae isolates, including 4.3% ceftriaxone-resistant isolates, collected 2021-24 in eight WHO EGASP countries, including five Asian countries, is high. Our findings support gepotidacin's continued clinical development, registration and introduction as a novel oral treatment for gonorrhoea. However, as with all new novel antimicrobials, cautious and optimal introduction, and surveillance of phenotypic and genomic susceptibility to gepotidacin internationally, pre- and post-licencing, should accompany any clinical implementation.
BACKGROUND:Klebsiella pneumoniae is the leading cause of sepsis among neonates in low- and middle-income countries (LMICs) in Africa and Asia, contributing substantially to the overall burden of antimicrobial-resistant infections and mortality among neonates globally. Pathogen sequencing has been used to investigate case clusters and confirm nosocomial transmission in a small number of neonatal units. Here we utilise pathogen sequence data to estimate the fraction of K. pneumoniae neonatal sepsis attributable to nosocomial transmission in African and South Asian countries. METHODS AND FINDINGS:We estimated the proportion of invasive K. pneumoniae disease involved in nosocomial transmission clusters in a given neonatal unit, using single-linkage clustering based on pairwise temporal and genetic distances estimated from bacterial whole-genome sequences aggregated from 10 contributing studies. Analysing 1,523 K. pneumoniae isolates from 27 units in 13 countries in Africa and South Asia between 2013 and 2023, we inferred 156 nosocomial transmission clusters, ranging from 2 to 188 neonates each (83 of the clusters comprised ≥3 cases). Overall, we estimated that 1,035 neonatal infections (68.0%) were part of nosocomial transmission clusters. Excluding the first infection in each cluster as a potential index case, we estimate at least 879 (57.7%) infections were acquired via nosocomial transmission. Sensitivity analyses showed that results were robust to the choice of genetic distance estimation methods and thresholds used to define clusters, and cluster estimates were stable over temporal distance thresholds ranging from 2 to 8 weeks. Isolates were mostly extended-spectrum beta-lactamase (ESBL) producers (90.9%) and included 172 multi-locus sequence types (STs). Fourteen STs, including several globally recognised multidrug-resistant lineages, were associated with transmission clusters at multiple units, and these were collectively responsible for two-thirds of all infections. Carriage of carbapenemase genes (adjusted odds ratio, aOR = 2.08 [95% confidence interval, CI: 1.04, 4.14]; p = 0.04) and ESBL genes (aOR = 2.48 [95% CI: 1.26, 4.90]; p = 0.006) were significantly positively associated with transmission in a logistic regression model with site as a covariate. Limitations of this study include the lack of sufficient clinical data to allow high-resolution investigation of transmission dynamics and lack of facility-level data to investigate contributors to the observed differences in transmission burden across sites. CONCLUSIONS:Nosocomial transmission contributes to a substantial proportion of K. pneumoniae sepsis in neonatal care units in Africa and South Asia. Reducing transmission within these settings through improved infection prevention and control and other measures could substantially reduce the neonatal sepsis burden. A high burden of transmission clusters is associated with the same drug-resistant lineages that are recognised as high-risk clones associated with hospital outbreaks in high-income countries, indicating global connectivity of the antimicrobial-resistant pathogen population.
