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Tropical infectious diseases inflict an unacceptable burden of disease on humans living in developing countries. Although anti-pathogenic drugs have been widely used, they carry a constant threat of selecting for resistance. Vaccines offer a promising means by which to enhance the global control of tropical infectious diseases; however, these have been difficult to develop, mostly because of the complex nature of the pathogen lifecycles. Here, we present recently developed vaccine candidates for five tropical infectious diseases in the form of a catalog that have either entered clinical trials or have been licensed for use. We deliberate on recently licensed dengue vaccines, provide evidence why combination vaccination could have a synergistic impact on schistosomiasis, critically appraise the value of typhoid conjugate vaccines, and discuss the potential of vaccines in the efforts to eliminate vivax malaria and hookworms.

Objectives: To determine the associated pathogen during the 2023 conjunctivitis outbreak in Vietnam Methods: RNA-sequencing was used to identify pathogens before and during the outbreak. Results: 24 patients with infectious conjunctivitis between March and October 2023 from Hai Yen Vision Institute in Vietnam were swabbed. Coxsackievirus A24v was the most common pathogen identified. Phylogenetic analysis of these strains demonstrates similarities to the Coxsackievirus identified in the 2022 India outbreak. Human adenovirus D was also circulating. Ocular findings of tearing, purulence, and itching were common in this outbreak. Conclusions: Multiple viruses can co-circulate during conjunctivitis outbreaks. Hemorrhagic conjunctivitis, commonly associated with coxsackievirus conjunctivitis, was not a common clinical sign in this outbreak. Repeat genetic surveillance, with the notable inclusion of RNA virus detection strategies, is important for outbreak detection.

Intro: Urinary tract infection (UTI) is one of the most common infections in children. Escherichia coli is the predominant organism causing UTI. The emergence of ESBL+ve E.coli harbouring other resistance genes poses a major challenge to clinicians. Though antimicrobial resistance (AMR) is of global concern, gathering local data in community-settings cannot be overemphasized. It is prudent to have knowledge about the genome of ESBL+ve E.coli at the country level to mitigate the risk in near future. Methods: Children (2-18 years) having UTI symptoms for less than a week in community health centres of Delhi, Bangalore, Jodhpur and Bhubaneswar representing north, south, west and east India were enrolled from 2019-2021. Phenotypic identification and antimicrobial susceptibility testing of the isolates causing significant bacteriuria was performed using MALDI-TOF and VITEK 2. Nineteen ESBL+ve E. coli isolates were analyzed by whole genome sequencing. Findings: 9.1% (42/461) of children were positive causing significant bacteriuria. [M:F 1:1, > 50% > 10 years]. E.coli was the predominant uropathogen (83.3%, 35/42) followed by Klebsiella pneumoniae (12%, 5/42), and Proteus spp. (4.7%, 2/42). Sixty percent of the E.coli isolates were ESBL producers. Genome sequence of the ESBL+ve E.coli was observed to carry large number of AMR genes such as blaNDM-5, blaOxa-1, blaCTX-M-15/14, AmpC, AAC(3)-IIa/IIc/Ib and others. ST131phylogroup was the most prevalent. Plasmid IncFIB and IncFIA found in more than 50% isolates. Composite transposon, IS26 was found in many isolates carrying blaOxa-1, blaNDM-5, blaCTX-M-15/14, blaTEM, aac(3′)-lb with at least 98% identity and coverage. Conclusion: Our data represents a large-scale nationwide community study among children indicating ESBL+ve E.coli isolates harbouring multidrug-resistant genes with high-risk clones. There is an urgent need for augmented surveillance at the local level for the recent knowledge of AMR patterns in the community; thereby preventing the imminent threat of an epidemic of AMR in near future.

Scrub typhus (caused by Orientia tsutsugamushi) is a neglected and underdiagnosed disease due to its non-specific clinical presentation and challenging diagnostics. We document the first study of direct diagnosis of scrub typhus from the blood sample of a patient by full-length 16S ribosomal RNA gene amplicon analysis using Oxford Nanopore sequencing.

Intro: Lipoarabinomanan (LAM) antigen which is secreted actively by Mycobacteria at the diseased site and in urine of the infected patient serves as an attractive biomarker to diagnose Tuberculosis (TB). Given the limitations of current diagnostic modalities for Pleural TB which the second most common form of extrapulmonary TB in India, current study evaluated LAM's potential to serve as a point-of-care test to diagnose pleural TB. Methods: A pleural fluid specimen was subjected to LAM antigen detection using the lateral flow assay (LAM-LFA; make - Alere/Abott diagnostics) in addition to biochemical and microbiological assays, in a cross-sectional study on suspected pleural TB patients attending a tertiary care hospital in Chhattisgarh, India. The LAM-LFA test was also performed on an early morning urine sample from the same patient. LAM-LFA results were compared to microbiological reference standards/MRS (defined as Pleural TB confirmed by Mycobacterial culture or CBNAAT) and composite reference standards/CRS (Definite plus Probable TB – Clinico-radiologically diagnosed). Findings: Out of 170 evaluable subjects, 26 had Definite TB, 22 had Probable TB, and 122 had No TB. When compared to MRS and CRS, pleural LAM-LFA testing was found to be less sensitive (61.54% & 45.83%) with poor PPV (57.14% & 78.57%) but more specific (91.67% & 95.08%) with good NPV (92.96% & 81.69%). Except for having higher specificity (97.2% and 98.3%, respectively, against MRS and CRS), urinary LAM-LFA performed worse than pleural LAM-LFA. When the subgroup of patients with significant ADA levels (ROC derived cut off value = 40 IU/ml) was studied, the specificity and PPV of pleural LAM detection increased to 100% each. Conclusion: Detection of LAM antigen by LFA directly from pleural fluid performed fairly accurate in diagnosing pleural TB and was highly predictive of the disease in a selected cohort of patients making it a valuable POCT.

Intro: Dengue, a vector-borne disease, is a global threat to public health with incidence increased from 0.5 to 5.2 million cases between 2010 and 2019. Data collected over ∼57 months of the phase-3 DEN-301 trial of the candidate vaccine (TAK-003) demonstrated long-term efficacy against symptomatic and hospitalized dengue. The objective of the present study was to assess the disease impact and cost-effectiveness of vaccination with two doses of TAK-003 in Thailand. Methods: A deterministic compartmental dynamic model of dengue transmission was developed to explicitly model host and vector populations, seasonality, and up to four serotype-specific infections. It was fitted to the dengue incidence observed in Thailand accounting for under-reporting. The disease impact and cost-effectiveness of vaccination were assessed over a 20- year time horizon. Vaccination strategies included routine vaccination of 11-year- olds, and routine with catch-up campaigns of 5, 10 or 20 age cohorts, respectively. Vaccine efficacy was derived and extrapolated from the TAK-003 phase-3 pivotal efficacy DEN-301 trial. Findings: Routine vaccination at age 11 with TAK-003 prevented 41% of symptomatic cases and 50% of hospitalized cases in Thailand, which translated to 138,783 DALYs averted. Routine with catch-up campaigns of 5, 10 and 20 age- cohorts resulted in a reduction of symptomatic cases by 46%, 49% and 55%, respectively, and hospitalized cases by 57%, 62% and 69%, respectively. All vaccination strategies were cost-saving compared to no vaccination and could lead to cost-savings of US$1.9 million - $1.6 billion (across a price range of 25$-60$/dose) over 20 years from the societal perspective where both medical costs and patients’ out-of-pocket costs and productivity loss were considered. Conclusion: Routine vaccination with TAK-003 could lead to significant reductions of symptomatic and hospitalized dengue along with considerable societal and healthcare cost-savings in Thailand. The impact could be even larger when catch-up campaigns of broader age cohorts were considered.

Intro: Leprosy Type 1 Reaction (T1R) is a chronic inflammatory disorder involving dysregulation between T helper cells, particularly Th17 and Tregs, has been postulated in earlier investigations to be responsible for T1R responses. ILCs (innate lymphoid cells) are predominantly present in the skin and are known to modulate Th17 and Tregs cells. Thus, understanding the pathogenic involvement of ILCs in T1R would offer fresh perspective on the intervention and therapy of T1R reactions. Methods: The study included 20 T1R and 20 non-reaction (NR) patients. By using flowcytometry, we identified both ILC3s and ILCregs, in the MLSA stimulated PBMCs. In-situ skin gene expression of cytokines (IL-17A and TGF-β) was further examined using qPCR. Findings: T1R had significantly (p

Intro: Cefiderocol is a siderophore cephalosporin and recently FDA-approved drug possessing potent activity against carbapenem-resistant gram-negative bacilli (CR-GNB) (Enterobacterales, and Nil-fermenter) due to its modified structure, iron-chelation mechanism, stability to hydrolysis by nearly all β-lactamases (including Metallo beta-lactamases and AmpC), overcoming capacity against efflux pump overexpression and porin channels mutations. This is the first study from India evaluating in-vitro susceptibility of Cefiderocol against CRGNBs. Methods: A prospective observational study was conducted at a tertiary care hospital in India during 2021-2022. CR-GNB isolates from patients with bloodstream infection, urinary tract infection, and pneumonia were tested for Cefiderocol in-vitro susceptibility using broth microdilution technique (BMD) as per CLSI 2022 guideline. Two Acinetobacter baumanii (AB) isolates observed resistant to Cefiderocol (MIC>32mg/ml) were further analysed by whole genome sequencing (WGS). Findings: Forty CR-GNB isolates were tested for BMD [5: Escherichia coli (EC), 7: Pseudomonas aeruginosa (PA), 13: Klebsiella pneumoniae (KP) and 15: Acinetobacter baumanii (AB)]. The susceptibility of EC, PA, KP and AB against Cefiderocol was observed as 60%, 43%, 100%, and 13.3% respectively. Approximately, 20% of EC isolates and 28.5% of PA isolates showed intermediate susceptibility using BMD. All the AB isolates from respiratory specimens were observed resistant to Cefiderocol (MIC > 32mg/ml). On WGS analysis, the two resistant AB isolates were found to harbour blaPER-7 in combination with blaOXA-23/blaNDM- 1 along with other carbapenemase genes blaOXA-66 & blaOXA-68. Conclusion: In our study, Cefiderocol was found to have potent in-vitro activity against K. pneumoniae, in comparison to other CR-GNB. Higher resistance was seen in A. baumanii isolates, which might be attributed to the synergistic effect of PER-7 type of beta-lactamases in presence of blaOXA-23 and blaNDM-1 gene.

Objectives: Although extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) are a global challenge, data on these organisms in low- and middle-income countries are limited. In this study, we sought to characterize colonization data critical for greater antibiotic resistance surveillance efforts. Methods: This study was conducted in three hospitals and six clinics in Botswana. We conducted ongoing surveillance of adult patients in hospitals and clinics and adults and children in the community. All participants underwent rectal swab sampling to identify ESCrE and CRE. Results: Enrollment occurred from January 15, 2020, to September 4, 2020, but paused from April 2, 2020, to May 21, 2020, because of a countrywide COVID-19 lockdown. Of 5088 individuals approached, 2469 (49%) participated. ESCrE colonization prevalence was 30.7% overall (43% for hospital participants, 31% for clinic participants, 24% for adult community participants, and 26% for child community participants) (P

Objectives: This study aimed to assess the processes and clinical outcomes of a joint collaboration between Antimicrobial Stewardship Program (ASP) and the outpatient parenteral antimicrobial therapy (OPAT) unit for delivery of monoclonal antibody therapy for mild-to-moderate COVID-19. Methods: We carried out a retrospective, interim analysis of our COVID-19 monoclonal antibody therapy program. Outcomes included clinical response, incidence of hospitalization, and adverse events. Results: A total of 175 patients (casirivimab-imdevimab, n = 130; bamlanivimab, n = 45) were treated between December 2020 and March 1, 2021. The median time from symptom onset was 6 (IQR 4, 8) days at time of treatment. Of 135 patients available for follow-up, 71.9% and 85.9% of patients reported symptom improvement within 3 and 7 days of treatment, respectively. A total of 9 (6.7%) patients required COVID-19–related hospitalization for progression of symptoms, all within 14 days of treatment. A total of 7 (4%) patients experienced an infusion-related reaction. Conclusions: ASP-OPAT collaboration is a novel approach to implement an efficient and safe monoclonal antibody therapy program for the treatment of mild-to-moderate COVID-19.

Background: Between December 2013 and June 2016, West Africa experienced the largest Ebola virus disease (EVD) outbreak in history. Understanding EVD in pregnancy is important for EVD clinical screening and infection prevention and control. Methods: We conducted a review of medical records and EVD investigation reports from three districts in Sierra Leone. We report the clinical presentations and maternal and fetal outcomes of six pregnant women with atypical EVD, and subsequent transmission events from perinatal care. Results: The six women (ages 18–38) were all in the third trimester. Each presented with signs and symptoms initially attributed to pregnancy. None met EVD case definition; only one was known at presentation to be a contact of an EVD case. Five women died, and all six fetuses/neonates died. These cases resulted in at least 35 additional EVD cases. Conclusions: These cases add to the sparse literature focusing on pregnant women with EVD, highlighting challenges and implications for outbreak control. Infected newborns may also present atypically and may shed virus while apparently asymptomatic. Pregnant women identified a priori as contacts of EVD cases require special attention and planning for obstetrical care.

Objectives: The study aim was to describe the etiological profile and clinical characteristics of pneumonia among children hospitalized in Thimphu, Bhutan. Methods: This prospective study enrolled children aged 2–59 months admitted to the Jigme Dorji Wangchuck National Referral Hospital with World Health Organization (WHO)-defined clinical pneumonia. Demographic and clinico-radiological data were collected through questionnaires, physical examination, and chest radiography. Blood samples and nasopharyngeal washing were collected for microbiological analysis including culture and molecular methods. Results: From July 2017 to June 2018, 189 children were enrolled, of which 53.4% were infants. Pneumonia-related admissions were less frequent over the winter. Chest radiographies were obtained in 149 children; endpoints included pneumonia in 39 cases (26.2%), other infiltrates in 31 (20.8%), and were normal in 79 children (53.0%). Non-contaminated bacterial growth was detected in 8/152 (5.3%) blood cultures, with only two cases of Streptococcus pneumoniae. Viral detection in upper respiratory secretions was common, with at least one virus detected in 103/115 (89.6%). The three most-commonly isolated viruses were respiratory syncytial virus (52/115; 45.2%), rhinovirus (42/115; 36.5%), and human parainfluenza virus (19/115; 16.5%). A third of patients with viral infections showed mixed infections. Case fatality rate was 3.2% (6/189). Conclusion: Respiratory viral infections predominated among this cohort of WHO-defined clinical pneumonia cases, whereas bacterial aetiologies were uncommon, highlighting the epidemiologic transition that Bhutan seems to have reached.

Background: Scrub typhus has emerged as a major cause of acute febrile illness in India in recent years. The causative agent, Orientia tsutsugamushi has more than 20 prototype strains due to a variable 56-kDa outer membrane protein. It is crucial to know the prevailing types in India for the success of diagnostic immunoassays and prospective vaccine candidates. In north India, the principal types circulating are largely unknown. Our tertiary care hospital caters to a large area of north India (around 7 states and one union territory). Therefore, the current study was planned to identify the genotypes of O. tsutsugamushi strains circulating in this wide area of north India. Materials and methods: Adults and children presenting with suspected scrub typhus between July 2013 and December 2013 were included in this study. DNA was extracted from whole blood and a nested PCR was used to amplify a 483-bp region of the 56-kDa antigen gene of O. tsutsugamushi. The PCR products were purified and DNA sequencing was performed and aligned using the CLUSTAL_X2 program. A phylogenetic tree was constructed using neighbour- joining algorithms and analysed using the sequences obtained in this study and those obtained from the GenBank database. Results: A total of 34 samples were positive for PCR. The amplicons were sequenced and analyzed. Karp-like strains predominated in all states studied (64.7%) followed by Gilliam-like (26.47 %) and 8.82% similar to Hualien 1 or S072. We did not find any Kato or Kawasaki-like strain. Karp like strains showed >99% similarity to TH2033, TH2191, TH2208, Xinjiang & Neimeng strains and Gilliam-like strains showed >99% similarity to Clone ISS -11. Conclusion: Orientia tsutsugamushi shows a great diversity in its strains over a large geographical area of north India. This has implications in the production of both diagnostic assays and vaccine for scrub typhus. Keywords: Scrub typhus, Orientia tsutsugamushi, Eschar, North India

Background: Information about antimicrobial use is scarce and poorly understood among neonatal intensive care units (NICUs) in India. In this study, we describe antimicrobial use in eight NICUs using four point prevalence surveys (PPSs). Methods: As part of the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children (GARPEC) study, one-day, cross-sectional, hospital-based PPSs were conducted four times between 1 February 2016 and 28 February 2017 in eight NICUs. Using a standardized web-based electronic data entry form, detailed data were collected for babies on antimicrobials. Results: A total of 403 babies were admitted to NICUs across all survey days, and 208 (51.6%) were prescribed one or more antimicrobials. Among 208 babies, 155 (74.5%) were prescribed antimicrobials for treatment of an active infection. Among 155 babies with an active infection, treatment was empiric in 109 (70.3%). Sepsis (108, 49.1%) was the most common reason for prescribing antimicrobials. Amikacin (17%) followed by meropenem (12%) were the two most commonly prescribed antimicrobials. For community-acquired sepsis, piperacillin-tazobactam (17.5%) was the most commonly prescribed drug. A combination of ampicillin and gentamicin was prescribed in only two babies (5%). Conclusions: The recommended first-line antimicrobial agents, ampicillin and gentamicin, were rarely prescribed in Indian NICUs for community acquired neonatal sepsis.

Objectives: To assess the prevalence of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) co-infections among people living with HIV (PLHIV) in Nepal. Methods: A sample of 677 PLHIV representing key affected populations (KAP) in Nepal, who were undergoing antiretroviral (ART) therapy in ART clinics around the country, were voluntarily enrolled in the study. Rapid kit-based testing followed by ELISA for validation was performed, focusing on HBV surface antigen (HBsAg) and antibodies against HCV (anti-HCV). A multivariate logistic regression model was used to identify factors associated with HBV and HCV co-infection. Results: HCV and HBV co-infection among the 677 PLHIV was found to be 19% (95% confidence interval (CI) 16.6–22.7%) and 4.4% (95% CI 3.1–6.6%), respectively. The Eastern Region had the highest percentage of HCV infection (48%). The age group with the highest rates of co-infection was 30–39 years (58% and 70%, respectively, for HCV and HBV co-infection). After adjusting for confounding, males were more likely to have HBV co-infection than females (adjusted odds ratio (AOR) 4.61, 95% CI 1.42–14.98). Similarly, PLHIV who were male (AOR 5.7, 95% CI 2.06–15.98), had a secondary level of education (AOR 3.04, 95% CI 1.06–8.70), or who were drug users (AOR 28.7, 95% CI 14.9–55.22) were significantly more likely to have HCV co-infection. Conclusion: This first ever national assessment of HIV, HBV, and HCV co-infection performed among PLHIV in Nepal demonstrates that HCV and HBV infections are a health threat to this population and that interventions are required to mitigate the effects of co-infection and to prevent further morbidity and mortality.

Background: Dengue surveillance data in India are limited and probably substantially underestimate the burden of disease. A community-based study was undertaken to assess the prevalence of dengue-specific immunoglobulin G (IgG) antibodies in children across India and to examine historical dengue exposure rates. Potential associations between socio-economic factors and dengue seroprevalence were also assessed (registered at ctri.nic.in: CTRI/2011/12/002243). Methods: A convenience sample of 2609 healthy children aged 5–10 years was enrolled; these children were registered at or were living in the vicinity of eight centres located at six geographically distinct sites across India. Blood samples were drawn to test for the presence of dengue IgG antibodies using ELISA. Serotype-specific neutralizing antibody titres were measured in dengue IgG-positive children using dengue plaque reduction neutralization tests. Socio-demographic and household information was collected using a questionnaire. Results: Overall, 2558/2609 children had viable samples with laboratory results for dengue IgG. Dengue IgG seroprevalence across all sites was 59.6% (95% confidence interval 57.7–61.5%): the lowest (23.2%) was in Kalyani, West Bengal, and the highest (80.1%) was in Mumbai. Seroprevalence increased with age. Multivariate analysis suggested associations with household water storage/supply and type of housing. Half of the subjects with positive IgG results presented a multitypic profile, indicating previous exposure to more than one serotype. Conclusions: The overall dengue seroprevalence suggests that dengue endemicity in India is comparable to that in highly endemic countries of Southeast Asia. Additional prospective studies are required to fully quantify the disease burden, in order to support evidence-based policies for dengue prevention and control in India.

Background: The Indian population is facing highest dengue burden worldwide supporting an urgent need for vaccines. For vaccine introduction, evaluation and interpretation it is important to gain a critical understanding of immune memory induced by natural exposure. However, immune memory to dengue remains poorly characterized in this region. Methods: We enumerated levels of dengue specific memory B cells (MBC), neutralizing (NT) and binding antibodies in healthy adults (n = 70) from New Delhi. Results: NT-antibodies, binding antibodies and MBC were detectable in 86%, 86.56% and 81.63% of the subjects respectively. Among the neutralizing positive subjects, 58%, 27%, 5% and 10% neutralized all four, any three, any two and any one dengue serotypes respectively. The presence of the neutralizing antibodies was associated with the presence of the MBC and binding antibodies. However, a massive interindividual variation was observed in the levels of the neutralizing antibodies (range,

Background: Antibiotic resistance in enteric fever continues to pose major therapeutic challenge with increase in ciprofloxacin resistance. Azithromycin has been used to treat enteric fever as an alternate treatment option without any guidelines for laboratory interpretation. In 2015 issue CLSI has added breakpoints for testing azithromycin susceptibility in typhoidal Salmonellae. We aimed to assess the prevalence of resistance to azithromycin in S. Typhi and S. Paratyphi A in a collection of strains to characterize the mechanisms underlying resistance. Methods & Materials: A total number of 224 S. Typhi and S. Paratyphi A isolates were available in the cryopreservated stock which were isolated from the patients presented with enteric fever during 1990 to 2015. Antimicrobial susceptibility testing was done by disk diffusion method as per CLSI 2015 and MICs were determined by E test method as per manufacturer's guidelines (AB Biodisk, Sweden). For molecular chaeacterization of azithromycin resistance, PCR detection was done to screen for the presence of genes responsible for azithromycin resistance i.e, ereA, ereB, ermB, mefA, mphA, mphB and mphD from plasmid and genomic DNA. Sequence analysis was done to detect mutations in acrR, rlpD and rlpV from genomic DNA. Results: It was observed that 96.11% of the isolates were susceptible to azithromycin using disk diffusion method. There was a linear trend observed with time in azithromycin susceptibility (X² = 5.240, P value <0.02). The MIC 50 and MIC 90 values were 6 and 12μg/ml respectively while the resistance breakpoint is ≥16μg/ml. There was no acquired gene for macrolide resistance in plasmid or genomic DNA of any isolate and DNA sequences of acrR, rlpD and rlpV genes did not show any mutations. Total use of azithromycin in pediatric population was only 13,125 mg given to 16 patients in 2014-15. Conclusion: Azithromycin is a good promising agent against typhoid fever on the basis of MIC distribution in India at present. More studies are required to study the use of azithromycin in complicated infections as at present it is being used only for uncomplicated cases. [ABSTRACT FROM AUTHOR]

Objective: To test efficacy, safety and tolerability of Umifenovir in non-severe COVID-19 adult patients. Methods: We carried out randomized, double-blind, placebo-controlled, multicenter, phase III trials involving adult (18-75 years), non-severe COVID19 patients, randomized 1:1 on placebo or Umifenovir (800 mg BID, maximum 14 days) respectively along with standard-of-care. The primary endpoint for Asymptotic-mild patients was time to nasopharyngeal swab RT-PCR test negativity. For Moderate patients, the average change in the ordinal scale from the baseline scores on the eight-point WHO ordinal scale was assessed. Results: 132 patients were recruited between 3rd October to 28th April 2021, of which 9 discontinued due to various reasons. In Mild-asymptomatic patients (n=82), we found that 73% patients in the Umifenovir arm were RT-PCR negative, while 40% patients in the placebo arm were negative (P=0.004) on day 5. However, in the moderate group (n=41), the WHO scores for the Umifenovir arm was not statistically significant (P=0.125 on day 3), while it was statistically significant in the Mild-asymptomatic group (P=0.019 on day 5). Conclusion: Umifenovir meets the primary and secondary endpoint criteria and exhibits statistically significant efficacy for Mild-asymptomatic patients. It is efficacious, safe and well-tolerated at the tested dosage of 800mg BID, maximum 14 days.

Placental malaria is a public health burden particularly in Africa as it causes severe symptoms and results in stillbirths or maternal deaths. Plasmodium falciparum protein VAR2CSA drives placental malaria (PM) in pregnant women by adhering to chondroitin sulfate A (CSA) on the placenta. VAR2CSA is a primary vaccine candidate for PM with two vaccines based on it already under clinical trials. The first cryo-EM three-dimensional structure of Pf CSA-VAR2CSA complex revealed crucial interacting residues considered to be highly conserved across P. falciparum strains. In the current study, we have conducted a global sequence analysis of 1,114 VAR2CSA field isolate sequences from more than nine countries across three continents revealing numerous mutations in CSA-binding residues. Further, structural mapping has revealed significant polymorphisms on the ligand binding surfaces. The variants from this limited set of 1,114 sequences highlight the concerns that are vital in current considerations for development of vaccines based on VAR2CSA for placental malaria.

Objective: In the fight against COVID-19, vaccination is vital in achieving herd immunity. Many Asian countries are starting to vaccinate frontline workers; however, expedited vaccine development has led to hesitancy among the general population. We evaluated the willingness of healthcare workers to receive the COVID-19 vaccine. Methods: From 12 to 21 December 2020, we recruited 1720 healthcare workers from 6 countries: China, India, Indonesia, Singapore, Vietnam and Bhutan. The self-administrated survey collected information on willingness to vaccinate, perception of COVID-19, vaccine concerns, COVID-19 risk profile, stigma, pro-socialness scale, and trust in health authorities. Results: More than 95% of the healthcare workers surveyed were willing to vaccinate. These respondents were more likely to perceive the pandemic as severe, consider the vaccine safe, have less financial concerns, less stigmatization regarding the vaccine, higher pro-socialness mindset and trust in health authorities. A high perceived pandemic risk index, low vaccine harm index and high pro-socialness index were independent predictors in multivariable analysis. Conclusions: The majority of healthcare workers in Asia are willing to receive COVID-19 vaccination. Perceived COVID-19 susceptibility, low potential risk of vaccine harm and pro-socialness are the main drivers. These findings may help formulate vaccination strategies in other countries.

ABSTRACT: Objectives: A retrospective study was undertaken to investigate the circulating dengue virus (DENV) serotypes and genotypes in India in 2018. Methods: In total, 4963 samples referred to virus research diagnostic laboratories (n=21), the Indian Council of Medical Research-National Institute of Virology (ICMR-NIV) and ICMR-NIV field units (n=2) for diagnosis of dengue in 2018 were tested using a real-time reverse transcription polymerase chain reaction assay for the presence of DENV serotypes. Representative samples were sequenced for the envelope (E) gene. Results: Regional diversity was observed with regard to the dominant circulating serotypes. DENV-2 was found to be the most common serotype in many states. Thrombocytopenia, petechiae and malaise were associated with DENV-2 infection. Phylogenetic analyses of DENV E gene sequences revealed the circulation of genotypes I and V of DENV-1, two lineages of DENV-2 genotype IV, DENV-3 genotype III and DENV-4 genotype I. Conclusions: This study found regional differences in the prevalence of circulating DENV serotypes in India, and provides baseline data for continuous molecular surveillance. Molecular surveillance may have implications for predicting large-scale outbreaks of dengue if regional shifts in the predominantly circulating serotypes and genotypes are detected during the early phase of the dengue season.

Objective: To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG IFN-α2b) administered in conjunction with the standard of care (SOC) in subjects with moderate coronavirus disease-19 (COVID-19). Methods: In this study, adult subjects with confirmed moderate COVID-19 were randomized in a 1:1 ratio to receive either PEG IFN-α2b + SOC or SOC alone. The primary endpoint was a two-point improvement in clinical status on Day 11, measured by the World Health Organization's seven-point ordinal scale. Results: Of 250 subjects, 120 were randomized to the PEG IFN-α2b + SOC arm and 130 were randomized to the SOC arm. The results for the PEG IFN + SOC arms vs the SOC arm for the proportion of subjects with a two-point improvement in the seven-point ordinal scale were 80.36% vs 68.18% (P=0.037) on Day 8, 91.60% vs 92.56% (P=0.781) on Day 11, and 94.12% vs 95.93% (P=0.515) on Day 15. There was a time-dependent decrease in the biomarkers in both arms, and no clinically significant changes in laboratory parameters. The safety profile was similar in both arms. Conclusion: PEG IFN-α2b induced early viral clearance, improved the clinical status, and decreased the duration of supplemental oxygen. It provides a viable treatment option and can limit the spread of severe acute respiratory syndrome coronavirus-2.

Background: Earlier serosurveys in India revealed seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) of 0.73% in May–June 2020 and 7.1% in August–September 2020. A third serosurvey was conducted between December 2020 and January 2021 to estimate the seroprevalence of SARS-CoV-2 infection among the general population and healthcare workers (HCWs) in India. Methods: The third serosurvey was conducted in the same 70 districts as the first and second serosurveys. For each district, at least 400 individuals aged ≥10 years from the general population and 100 HCWs from subdistrict-level health facilities were enrolled. Serum samples from the general population were tested for the presence of immunoglobulin G (IgG) antibodies against the nucleocapsid (N) and spike (S1-RBD) proteins of SARS-CoV-2, whereas serum samples from HCWs were tested for anti-S1-RBD. Weighted seroprevalence adjusted for assay characteristics was estimated. Results: Of the 28,598 serum samples from the general population, 4585 (16%) had IgG antibodies against the N protein, 6647 (23.2%) had IgG antibodies against the S1-RBD protein, and 7436 (26%) had IgG antibodies against either the N protein or the S1-RBD protein. Weighted and assay-characteristic-adjusted seroprevalence against either of the antibodies was 24.1% [95% confidence interval (CI) 23.0–25.3%]. Among 7385 HCWs, the seroprevalence of anti-S1-RBD IgG antibodies was 25.6% (95% CI 23.5–27.8%). Conclusions: Nearly one in four individuals aged ≥10 years from the general population as well as HCWs in India had been exposed to SARS-CoV-2 by December 2020.

Complementing whole genome sequencing strategies with high-throughput multiplex RT-qPCR genotyping allows for more comprehensive and real-time tracking of SARS-CoV-2 variants of concern. During the second and third waves of COVID-19 in Qatar, PCR genotyping, combined with Sanger sequencing of un-typeable samples, was employed to describe the epidemiology of the Alpha, Beta and Delta variants. A total of 9792 nasopharyngeal PCR-positive samples collected between April-June 2021 were successfully genotyped, revealing the importation and transmission dynamics of these three variants in Qatar.

Background: Worldwide, seasonal influenza causes significant mortality and poses a significant economic burden. Oseltamivir is an effective treatment, but benefits beyond immediate hospitalization are unknown. Methods: This retrospective multicenter study included adult hospitalized influenza patients from two major teaching hospitals in Australia. Patients who received Oseltamivir 48 h (delayed/no-treatment group). Propensity-score matching was used to balance confounders between two groups. Primary outcomes included 30-day readmissions, 30-day mortality, composite-outcome (30-day mortality and readmissions), in-hospital mortality, and hospital length of stay (LOS). Results: Between January 2016–March 2020, 1828 adult patients mean (SD) age 66.4 (20.1), 52.9% females, were hospitalized with influenza. Four hundred and forty-eight (24.5%) received prompt-treatment with Oseltamivir, while 1380 (75.5%) patients were in the delayed/no-treatment group. The median (IQR) time from onset of symptoms to the administration of Oseltamivir was three (1–5) days. The propensity-score model included 245 matched patients in each group (standardized mean difference of

Objectives: The recent discoveries of phylogenetically confirmed COVID-19 reinfection cases worldwide, together with studies suggesting that antibody titres decrease over time, raise the question of what course the epidemic trajectories may take if immunity were really to be temporary in a significant fraction of the population. The objective of this study is to obtain an answer for this important question. Methods: We construct a ground-up delay differential equation model tailored to incorporate different types of immune response. We considered two immune responses: (a) short-lived immunity of all types, and (b) short-lived sterilizing immunity with durable severity-reducing immunity. Results: Multiple wave solutions to the model are manifest for intermediate values of the reproduction number R; interestingly, for sufficiently low as well as sufficiently high R, we find conventional single-wave solutions despite temporary immunity. Conclusions: The versatility of our model, and its very modest demands on computational resources, ensure that a set of disease trajectories can be computed virtually on the same day that a new and relevant immune response study is released. Our work can also be used to analyse the disease dynamics after a vaccine is certified for use and information regarding its immune response becomes available.

Background: An increasing number of patients with cutaneous leishmaniasis (CL) are reporting to tertiary care centers in Jammu and Kashmir, an area that has previously been non-endemic for this disease. This merits consideration of CL as a major health problem of considerable epidemiological importance. The aims of this study were firstly to describe the clinico-epidemiological profile, therapeutic characteristics, and outcomes of patients with CL and secondly to highlight this union territory as a new focus of endemicity for CL. Methods: A two-center hospital-based prospective cohort study was conducted at two tertiary care hospitals in Jammu and Kashmir over a period of 10 years (July 2009 to June 19). All patients presenting to the outpatient departments with lesions suggestive of CL were enrolled for the purpose of this study. Demographic data were recorded on a proforma questionnaire, along with a detailed history and the results of a meticulous examination. Patients diagnosed with CL based on clinical criteria were subjected to slit skin smear (SSS) and histopathological examination for confirmation of the diagnosis. An intralesional pentavalent antimonial, sodium stibogluconate (SSG), was administered at a dose of 0.5 mL/cm2 (100 mg/mL solution) three times weekly to those patients with smaller lesions, and intravenously or intramuscularly at a dose of 20 mg/kg/day to those with larger lesions. The response to treatment was assessed by total re-epithelialization of the lesion and an absence of infiltration and erythema, with or without scarring. Treatment was given until complete resolution of the lesions or for a maximum duration of 10 weeks when given intralesionally and 3 weeks when given systemically. Clinical follow-up was performed twice weekly for the first 2 months and monthly thereafter. The final response to treatment was assessed at 6 months. Results: The study included a total of 1300 patients with a mean age of 26.7 ± 18.5 years. The mean duration of the disease was 28.52 ± 13.5 weeks, ranging from 8 to 64 weeks. Lesions were noted mainly on exposed parts of the body, with the face being the most commonly affected site (89.00%). Nodulo-ulcerative plaques were the predominant lesion type observed (73.92%). The presence of Leishman–Donovan bodies could be demonstrated on SSS and histopathology in 60.69% and 39.54% of patients, respectively. The presence of a recognizable histological pattern conforming to CL and a response to a therapeutic trial of SSG was considered to be confirmatory in the remaining patients. Complete cure was achieved in 84.23% of cases during the study period. Single lesions were more likely to respond to treatment as compared to multiple lesions. The route of administration did not have any significant impact on the final outcome. Conclusions: With the disease showing an escalating trend in Jammu and Kashmir, the possibility of a new focus of endemicity and its impact on public health need to be contemplated, and appropriate measures should be initiated to contain its spread.

Background: Plasmodium falciparum erythrocyte membrane protein is encoded by a highly variable multicopy var gene family known to play a key role in malaria pathogenicity. Therefore, we investigated sequence variation, expression profile and immune response of the Duffy binding-like domain (DBLα) region of the var gene. Methods: Blood samples were collected from patients with cerebral, severe and mild malaria in Chhattisgarh, India, a region with endemic malaria. Polymerase chain reaction amplicons were cloned and sequenced to determine sequence variation. The expression level was analyzed targeting the upstream region of var gene using the Delta-Delta-Ct method. Immunoglobulin G (IgG) level was determined against the 6 synthetic peptides of the DBLα region. Results: The study identified that group 1 and group 5 sequences (cysteine/position of limited variability (cys/PoLV) classification) along with cys2/cys4 and MFK*/REY motifs and short amino acid length were significantly associated with malaria severity. The specific PoLV (MFKS, LREA, PTNL) were restricted to cerebral malaria. The expression level of var group A was higher than var groups B and C, demonstrating its prognostic characteristic. All peptides showed high-quality IgG response, while VAR P5 appeared to be a good marker for severity. Conclusions: The present study illustrates the presence of specific sequences of DBLα tags involved in severe malaria that could be targeted in future interventions for malaria control and elimination.