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Health-care-associated infections (HAIs) cause significant morbidity and mortality globally, including in low-income and middle-income countries (LMICs). Networks of hospitals implementing standardised HAI surveillance can provide valuable data on HAI burden, and identify and monitor HAI prevention gaps. Hospitals in many LMICs use HAI case definitions developed for higher-resourced settings, which require human resources and laboratory and imaging tests that are often not available.A network of 26 tertiary-level hospitals in India was created to implement HAI surveillance and prevention activities. Existing HAI case definitions were modified to facilitate standardised, resource-appropriate surveillance across hospitals. Hospitals identified health-care-associated bloodstream infections and urinary tract infections (UTIs) and reported clinical and microbiological data to the network for analysis.26 network hospitals reported 2622 health-care-associated bloodstream infections and 737 health-care-associated UTIs from 89 intensive care units (ICUs) between May 1, 2017, and Oct 31, 2018. Central line-associated bloodstream infection rates were highest in neonatal ICUs (20 per 1000 central line days). Catheter-associated UTI rates were highest in paediatric medical ICUs (4·5 per 1000 urinary catheter days). Klebsiella spp (24·8%) were the most frequent organism in bloodstream infections and Candida spp (29·4%) in UTIs. Carbapenem resistance was common in Gram-negative infections, occurring in 72% of bloodstream infections and 76% of UTIs caused by Klebsiella spp, 77% of bloodstream infections and 76% of UTIs caused by Acinetobacter spp, and 64% of bloodstream infections and 72% of UTIs caused by Pseudomonas spp.The first standardised HAI surveillance network in India has succeeded in implementing locally adapted and context-appropriate protocols consistently across hospitals and has been able to identify a large number of HAIs. Network data show high HAI and antimicrobial resistance rates in tertiary hospitals, showing the importance of implementing multimodal HAI prevention and antimicrobial resistance containment strategies.US Centers for Disease Control and Prevention cooperative agreement with All India Institute of Medical Sciences, New Delhi.For the Hindi translation of the abstract see Supplementary Materials section.

Background Despite significant global progress in reducing neonatal mortality, bacterial sepsis remains a major cause of neonatal deaths. Klebsiella pneumoniae (K. pneumoniae) is the leading pathogen globally underlying cases of neonatal sepsis and is frequently resistant to antibiotic treatment regimens recommended by the World Health Organization (WHO), including first-line therapy with ampicillin and gentamicin, second-line therapy with amikacin and ceftazidime, and meropenem. Maternal vaccination to prevent neonatal infection could reduce the burden of K. pneumoniae neonatal sepsis in low- and middle-income countries (LMICs) but the potential impact of vaccination remains poorly quantified. We estimated the potential impact of such vaccination on cases and deaths of K. pneumoniae neonatal sepsis and project the global effects of routine immunization of pregnant women with the K. pneumoniae vaccine as antimicrobial resistance (AMR) increases. Methods and findings We developed a Bayesian mixture-modeling framework to estimate the effects of a hypothetical K. pneumoniae maternal vaccine with 70% efficacy administered with coverage equivalent to that of the maternal tetanus vaccine on neonatal sepsis infections and mortality. To parameterize our model, we used data from 3 global studies of neonatal sepsis and/or mortality—with 2,330 neonates who died with sepsis surveilled from 2016 to 2020 undertaken in 18 mainly LMICs across all WHO regions (Ethiopia, Kenya, Mali, Mozambique, Nigeria, Rwanda, Sierra Leone, South Africa, Uganda, Brazil, Italy, Greece, Pakistan, Bangladesh, India, Thailand, China, and Vietnam). Within these studies, 26.95% of fatal neonatal sepsis cases were culture-positive for K. pneumoniae. We analyzed 9,070 K. pneumoniae genomes from human isolates gathered globally from 2001 to 2020 to quantify the temporal rate of acquisition of AMR genes in K. pneumoniae isolates to predict the future number of drug-resistant cases and deaths that could be averted by vaccination. Resistance rates to carbapenems are increasing most rapidly and 22.43% [95th percentile Bayesian credible interval (CrI): 5.24 to 41.42] of neonatal sepsis deaths are caused by meropenem-resistant K. pneumoniae. Globally, we estimate that maternal vaccination could avert 80,258 [CrI: 18,084 to 189,040] neonatal deaths and 399,015 [CrI: 334,523 to 485,442] neonatal sepsis cases yearly worldwide, accounting for more than 1.49% [CrI: 0.33 to 3.51] of all neonatal deaths. The largest relative benefits are in Africa (Sierra Leone, Mali, Niger) and South-East Asia (Bangladesh) where vaccination could avert over 5% of all neonatal deaths. Nevertheless, our modeling only considers country-level trends in K. pneumoniae neonatal sepsis deaths and is unable to consider within-country variability in bacterial prevalence that may impact the projected burden of sepsis. Conclusions A K. pneumoniae maternal vaccine could have widespread, sustained global benefits as AMR in K. pneumoniae continues to increase.

The Bill & Melinda Gates Foundation supported respiratory syncytial virus (RSV) mortality surveillance studies in several low- and middle-income countries to address the striking gap in community mortality burden data from these geographies. The compelling findings generated from these studies reveal a high unmeasured burden of community RSV mortality, particularly among infants aged

World Health Organization (WHO) preferred product characteristics describe preferences for product attributes that would help optimize value and use to address global public health needs, with a particular focus on low- and middle-income countries. Having previously published preferred product characteristics for both maternal and paediatric respiratory syncytial virus (RSV) vaccines, WHO recently published preferred product characteristics for monoclonal antibodies to prevent severe RSV disease in infants. This article summarizes the key attributes from the preferred product characteristics and discusses key considerations for future access and use of preventive RSV monoclonal antibodies.

Respiratory syncytial virus is the second most common cause of infant mortality and a major cause of morbidity and mortality in older adults (aged >60 years). Efforts to develop a respiratory syncytial virus vaccine or immunoprophylaxis remain highly active. 33 respiratory syncytial virus prevention candidates are in clinical development using six different approaches: recombinant vector, subunit, particle-based, live attenuated, chimeric, and nucleic acid vaccines; and monoclonal antibodies. Nine candidates are in phase 3 clinical trials. Understanding the epitopes targeted by highly neutralising antibodies has resulted in a shift from empirical to rational and structure-based vaccine and monoclonal antibody design. An extended half-life monoclonal antibody for all infants is likely to be within 1 year of regulatory approval ( from August, 2022) for high-income countries. Live-attenuated vaccines are in development for older infants (aged >6 months). Subunit vaccines are in late-stage trials for pregnant women to protect infants, whereas vector, subunit, and nucleic acid approaches are being developed for older adults. Urgent next steps include ensuring access and affordability of a respiratory syncytial virus vaccine globally. This review gives an overview of respiratory syncytial virus vaccines and monoclonal antibodies in clinical development highlighting different target populations, antigens, and trial results.

Objective:Resistance to colistin, a last resort antibiotic, has emerged in India. We investigated colistin-resistantKlebsiella pneumoniae(ColR-KP) in a hospital in India to describe infections, characterize resistance of isolates, compare concordance of detection methods, and identify transmission events.Design:Retrospective observational study.Methods:Case-patients were defined as individuals from whom ColR-KP was isolated from a clinical specimen between January 2016 and October 2017. Isolates resistant to colistin by Vitek 2 were confirmed by broth microdilution (BMD). Isolates underwent colistin susceptibility testing by disk diffusion and whole-genome sequencing. Medical records were reviewed.Results:Of 846K. pneumoniaeisolates, 34 (4%) were colistin resistant. In total, 22 case-patients were identified. Most (90%) were male; their median age was 33 years. Half were transferred from another hospital; 45% died. Case-patients were admitted for a median of 14 days before detection of ColR-KP. Also, 7 case-patients (32%) received colistin before detection of ColR-KP. All isolates were resistant to carbapenems and susceptible to tigecycline. Isolates resistant to colistin by Vitek 2 were also resistant by BMD; 2 ColR-KP isolates were resistant by disk diffusion. Moreover, 8 multilocus sequence types were identified. Isolates were negative for mobile colistin resistance (mcr) genes. Based on sequencing analysis, in-hospital transmission may have occurred with 8 case-patients (38%).Conclusions:Multiple infections caused by highly resistant,mcr-negative ColR-KP with substantial mortality were identified. Disk diffusion correlated poorly with Vitek 2 and BMD for detection of ColR-KP. Sequencing indicated multiple importation and in-hospital transmission events. Enhanced detection for ColR-KP may be warranted in India.

Phase 3 randomized-controlled trials have provided promising results of COVID-19 vaccine efficacy, ranging from 50 to 95% against symptomatic disease as the primary endpoints, resulting in emergency use authorization/listing for several vaccines. However, given the short duration of follow-up during the clinical trials, strict eligibility criteria, emerging variants of concern, and the changing epidemiology of the pandemic, many questions still remain unanswered regarding vaccine performance. Post-introduction vaccine effectiveness evaluations can help us to understand the vaccine's effect on reducing infection and disease when used in real-world conditions. They can also address important questions that were either not studied or were incompletely studied in the trials and that will inform evolving vaccine policy, including assessment of the duration of effectiveness; effectiveness in key subpopulations, such as the very old or immunocompromised; against severe disease and death due to COVID-19; against emerging SARS-CoV-2 variants of concern; and with different vaccination schedules, such as number of doses and varying dosing intervals. WHO convened an expert panel to develop interim best practice guidance for COVID-19 vaccine effectiveness evaluations. We present a summary of the interim guidance, including discussion of different study designs, priority outcomes to evaluate, potential biases, existing surveillance platforms that can be used, and recommendations for reporting results.

Annual outbreaks of acute encephalitis syndrome pose a major health burden in India. Although Japanese encephalitis virus (JEV) accounts for around 15% of reported cases, the aetiology of most cases remains unknown. We aimed to establish an enhanced surveillance network and to use a standardised diagnostic algorithm to conduct a systematic evaluation of acute encephalitis syndrome in India.In this large-scale, systematic surveillance study in India, patients presenting with acute encephalitis syndrome (ie, acute onset of fever with altered mental status, seizure, or both) to any of the 18 participating hospitals across Uttar Pradesh, West Bengal, and Assam were evaluated for JEV (serum and cerebrospinal fluid [CSF] IgM ELISA) per standard of care. In enhanced surveillance, JEV IgM-negative specimens were additionally evaluated for scrub typhus, dengue virus, and West Nile virus by serum IgM ELISA, and for Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, dengue virus, herpes simplex virus, and enterovirus by CSF PCR across five referral laboratories. In 2017, chikungunya and Leptospira serum IgM by ELISA and Zika virus serum and CSF by PCR were also tested.Of 10 107 patients with acute encephalitis syndrome enrolled in enhanced surveillance between Jan 1, 2014, and Dec 31, 2017, 5734 (57·8%) of 9917 participants with available data were male and 6179 (62·7%) of 9856 were children aged 15 years and younger. Among patients who provided a sample of either CSF or serum in enhanced surveillance, an aetiology was identified in 1921 (33·2%) of 5786 patients enrolled between 2014 and 2016 and in 1484 (34·3%) of 4321 patients enrolled in 2017. The most commonly identified aetiologies were JEV (1023 [17·7%] of 5786 patients), scrub typhus (645 [18·5%] of 3489), and dengue virus (161 [5·2%] of 3124). Among participants who provided both CSF and serum specimens, an aetiology was identified in 1446 (38·3%) of 3774 patients enrolled between 2014 and 2016 and in 936 (40·3%) of 2324 enrolled in 2017, representing a 3·1-times increase in the number of patients with acute encephalitis syndrome with an identified aetiology compared with standard care alone (299 [12·9%]; p0·0001).Implementation of a systematic diagnostic algorithm in an enhanced surveillance platform resulted in a 3·1-times increase in identification of the aetiology of acute encephalitis syndrome, besides JEV alone, and highlighted the importance of scrub typhus and dengue virus as important infectious aetiologies in India. These findings have prompted revision of the national testing guidelines for this syndrome across India.US Centers for Disease Control and Prevention.

SCOPUS: re.j, info:eu-repo/semantics/published

More than 85% of Covid-19 mortality in high income countries is among people 65 years of age or older. Recent disaggregated data from the UK and US show that minority communities have increased mortality among younger age groups and in South Africa initial data suggest that the majority of deaths from Covid-19 are under 65 years of age. These observations suggest significant potential for increased Covid-19 mortality among younger populations in Africa and South Asia and may impact age-based selection of high-risk groups eligible for a future vaccine.

Background: Healthcare-associated infections (HAIs) are a major global threat to patient safety. Systematic surveillance is crucial for understanding HAI rates and antimicrobial resistance trends and to guide infection prevention and control (IPC) activities based on local epidemiology. In India, no standardized national HAI surveillance system was in place before 2017. Methods: Public and private hospitals from across 21 states in India were recruited to participate in an HAI surveillance network. Baseline assessments followed by trainings ensured that basic microbiology and IPC implementation capacity existed at all sites. Standardized surveillance protocols for central-line–associated bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) were modified from the NHSN for the Indian context. IPC nurses were trained to implement surveillance protocols. Data were reported through a locally developed web portal. Standardized external data quality checks were performed to assure data quality. Results: Between May 2017 and April 2019, 109 ICUs from 37 hospitals (29 public and 8 private) enrolled in the network, of which 33 were teaching hospitals with >500 beds. The network recorded 679,109 patient days, 212,081 central-line days, and 387,092 urinary catheter days. Overall, 4,301 bloodstream infection (BSI) events and 1,402 urinary tract infection (UTI) events were reported. The network CLABSI rate was 9.4 per 1,000 central-line days and the CAUTI rate was 3.4 per 1,000 catheter days. The central-line utilization ratio was 0.31 and the urinary catheter utilization ratio was 0.57. Moreover, 3,542 (73%) of 4,742 pathogens reported from BSIs and 868 (53%) of 1,644 pathogens reported from UTIs were gram negative. Also, 1,680 (26.3%) of all 6,386 pathogens reported were Enterobacteriaceae. Of 1,486 Enterobacteriaceae with complete antibiotic susceptibility testing data reported, 832 (57%) were carbapenem resistant. Of 951 Enterobacteriaceae subjected to colistin broth microdilution testing, 62 (7%) were colistin resistant. The surveillance platform identified 2 separate hospital-level HAI outbreaks; one caused by colistin-resistant K. pneumoniae and another due to Burkholderia cepacia. Phased expansion of surveillance to additional hospitals continues. Conclusions: HAI surveillance was successfully implemented across a national network of diverse hospitals using modified NHSN protocols. Surveillance data are being used to understand HAI burden and trends at the facility and national levels, to inform public policy, and to direct efforts to implement effective hospital IPC activities. This network approach to HAI surveillance may provide lessons to other countries or contexts with limited surveillance capacity.Funding: NoneDisclosures: None

Resistance to colistin, a last resort antibiotic, has emerged in India. We investigated colistin-resistant Klebsiella pneumoniae(ColR-KP) in a hospital in India to describe infections, characterize resistance of isolates, compare concordance of detection methods, and identify transmission events.Retrospective observational study.Case-patients were defined as individuals from whom ColR-KP was isolated from a clinical specimen between January 2016 and October 2017. Isolates resistant to colistin by Vitek 2 were confirmed by broth microdilution (BMD). Isolates underwent colistin susceptibility testing by disk diffusion and whole-genome sequencing. Medical records were reviewed.Of 846 K. pneumoniae isolates, 34 (4%) were colistin resistant. In total, 22 case-patients were identified. Most (90%) were male; their median age was 33 years. Half were transferred from another hospital; 45% died. Case-patients were admitted for a median of 14 days before detection of ColR-KP. Also, 7 case-patients (32%) received colistin before detection of ColR-KP. All isolates were resistant to carbapenems and susceptible to tigecycline. Isolates resistant to colistin by Vitek 2 were also resistant by BMD; 2 ColR-KP isolates were resistant by disk diffusion. Moreover, 8 multilocus sequence types were identified. Isolates were negative for mobile colistin resistance (mcr) genes. Based on sequencing analysis, in-hospital transmission may have occurred with 8 case-patients (38%).Multiple infections caused by highly resistant, mcr-negative ColR-KP with substantial mortality were identified. Disk diffusion correlated poorly with Vitek 2 and BMD for detection of ColR-KP. Sequencing indicated multiple importation and in-hospital transmission events. Enhanced detection for ColR-KP may be warranted in India.

Background: Acute encephalitis syndrome (AES) surveillance in India has indicated that Japanese encephalitis virus (JEV) accounts for 5-35% of AES cases annually; the etiology remains unknown in the remaining cases. We implemented comprehensive AES surveillance to identify other etiological agents of AES, with emphasis on dengue virus. Methods: Serum and cerebrospinal fluid (CSF) specimens were collected from patients enrolled prospectively in AES surveillance from 2014-2017 at selected sites of three high burden states of India. All samples were initially tested for JEV IgM. Specimens negative for JEV by serology were tested for IgM to scrub typhus, dengue virus (DEN), and West Nile virus; all JEV IgM-negative CSF samples were tested by PCR for S. pneumoniae, N. meningitidis, H. influenzae, herpes simplex virus type 1, enteroviruses and DEN. Results: Of 10,107 AES patients, an etiology could be established in 49.2% of patients including JEV (16%), scrub typhus (16%) and DEN (5.2%) as the top three agents. Amongst the DEN positive cases (359/6892), seven (2%) were positive only for dengue virus RNA: one in serum and six in CSF. Conclusion: Amongst the pathogens identified, dengue accounted for 5% of all AES cases and was one of the three common etiological agents. These results underscore the importance of including dengue virus in routine testing of AES cases. Keywords: Acute encephalitis syndrome, Etiological agents, Dengue, India

Establishing and expanding government led networks to strengthen infection prevention and control and healthcare associated infection surveillance are essential to effectively tackle antimicrobial resistance. Soumya Swaminathan and colleagues discuss the progress in India

Summary Background Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the country's largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. Methods In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). Findings Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9·6 [95% CI 3·6 – 24]) and absence of an evening meal (2·2 [1·2–4·3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7·8 [95% CI 3·3–18·8], without evening meal; OR 3·6 [1·1–11·1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged from 44·9 μg/g to 220·0 μg/g. Interpretation Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks. Funding US Centers for Disease Control and Prevention.

Human immunodeficiency virus drug resistance (HIVDR) in cohorts of patients initiating antiretroviral therapy (ART) at clinics in Chennai and Mumbai, India, was assessed following World Health Organization (WHO) guidelines. Twelve months after ART initiation, 75% and 64.6% of participants at the Chennai and Mumbai clinics, respectively, achieved viral load suppression of

The World Health Organizations HIV Drug Resistance (WHO HIVDR) Threshold survey method was used to assess transmitted HIVDR in newly diagnosed HIV-1-infected primigravida women attending the Prevention of Parent to Child Transmission (PPTCT) centers in Kakinada, in whom it is likely that the infection had recently occurred. Out of the 56 consecutively collected eligible specimens, 51 were tested using the ViroSeq RT-PCR method (Abbott Germany) to obtain 47 consecutive sequences for the HIV-1 protease (PR) and reverse transcriptase (RT) region. As per the 2009 WHO list of mutations for surveillance of transmitted HIVDR, only one nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation was detected at K101E from all specimens tested, suggesting a low prevalence (5%) of resistance to NNRTIs and no mutations were detected at other sites, suggesting a low prevalence (5%) of resistance to nucleoside reverse transcriptase inhibitors (NRTI) and protease inhibitors (PI) drug classes as well. Phylogenetic analysis showed all sequences belonged to HIV-1 subtype C. In the wake of antiretroviral treatment (ART) scale-up, future evaluation of transmitted HIVDR is essential in Kakinada as well as in other regions of India.

(See the editorial commentary by Von Reyn, on pages 817–9.) The epidemics of tuberculosis and human immunodeficiency virus type 1 (HIV) infection converged with the greatest intensity in sub-Saharan Africa. Both the incidence and the prevalence of tuberculosis increased as the HIV infection epidemic swept through the continent. In Africa today, tuberculosis may affect up to 30% of coinfected persons [1] and is the leading cause of death. Even with effective antituberculosis treatment, case fatality rates for tuberculosis may be as high as 20%, especially in the face of severe immunosuppression [2, 3]. Moreover, tuberculosis may accelerate the clinical course of HIV infection and lead to poor outcomes [4–7]. Newly revised guidelines from the World Health Organization (WHO) recommend the use of antiretroviral therapy for all HIV-seropositive persons with tuberculosis disease, regardless of their CD4+ T-cell count [8]. Recent evidence indicates that antiretroviral therapy should be started early in the course of tuberculosis treatment because it improves survival [9, 10]. Although there is abundant information on the benefit of antiretroviral therapy in HIV-infected tuberculosis patients with advanced immunosuppression [11–13], there are fewer data on the optimal management of tuberculosis among patients with CD4+ T-cell counts of >350 cells/μL. The present study was designed in the early years of the antiretroviral therapy rollout in Africa to determine whether a 6-month course of antiretroviral therapy given concurrently with tuberculosis treatment would improve the clinical, immunologic, and virologic outcomes among patients with CD4+ T-cell counts of >350 cells/μL. The rationale of the study was that a punctuated course of antiretroviral therapy in patients with high CD4+ T-cell counts would suppress viral replication during therapy for tuberculosis, block the effects of immune activation on T cells harboring HIV, slow the pace of HIV disease progression, and improve clinical outcomes. Although treatment interruption is no longer a viable option given recent advances in the field of HIV infection management [14], the present study provides evidence of clinical benefit when starting antiretroviral therapy in tuberculosis patients with preserved immunity.

Background: There has been tremendous scale-up of antiretroviral therapy (ART) services in the Asia Pacific region, which is home to an estimated 4.7 million persons living with HIV/AIDS. We examined treatment scale-up, ART program practices, and clinical outcome data in the nine low-and-middle-income countries that share over 95% of the HIV burden in the region. Methods: Standardized indicators for ART scale-up and treatment outcomes were examined for Cambodia, China, India, Indonesia, Myanmar, Nepal, Papua New Guinea, Thailand, and Vietnam using data submitted by each country to the WHO/ The Joint United Nations Programme on HIV/AIDS (UNAIDS)/UNICEF joint framework tool for monitoring the health sector response to HIV/AIDS. Data on ART program practices were abstracted from National HIV Treatment Guidelines for each country. Results: At the end of 2009, over 700000 HIV-infected persons were receiving ART in the nine focus countries. Treatment coverage varies widely in the region, ranging from 16 to 93%. All nine countries employ a public health approach to ART services and provide a standardized first-line nonnucleoside reverse transcriptase inhibitor-based regimen. Among patients initiated on first-line ART in these countries, 65‐88% remain alive and on treatment 12 months later. Over 50% of mortality occurs in the first 6 months of therapy, and losses to follow-up range from 8 to 16% at 2 years. Conclusion: Impressive ART scale-up efforts in the region have resulted in significant improvements in survival among persons receiving therapy. Continued funding support and political commitment will be essential for further expansion of public sector ART services to those in need. To improve treatment outcomes, national programs should focus on earlier identification of persons requiring ART, decentralization of ART services, and the development of stronger healthcare systems to support the provision of a continuum of HIV care. 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2010, 24 (suppl 3):S62‐S71

In a prospective randomized, controlled trial in Uganda comparing the efficacy of antiretroviral therapy during tuberculosis therapy with the efficacy of tuberculosis therapy alone in HIV-infected patients with tuberculosis who have a CD4(+) cell count350 cells/microL, it was found that antiretroviral therapy did not accelerate microbiologic, radiographic, or clinical responses to tuberculosis therapy: 18% of participants had sputum smears positive for Mycobacterium tuberculosis after 5 months of tuberculosis therapy, despite having had negative culture results. Trial registration. ClinicalTrials.gov identifier: NCT00078247 .

Summary To develop better estimates of brucellosis incidence, we conducted population-based surveillance for acute febrile illness (AFI) in Fayoum governorate (population 2 347 249), Egypt during two summer periods (2002 and 2003). All hospitals and a representative sample of community healthcare providers were included. AFI patients without obvious etiology were tested for brucellosis by culture and serology. Incidence estimates were calculated adjusting for sampling methodology and study period. Of 4490 AFI patients enrolled, 321 (7%) met the brucellosis case definition. The estimated annual incidence of brucellosis per 100 000 population was 64 and 70 in 2002 and 2003, respectively. The median age of brucellosis patients was 26 years and 70% were male; 53% were initially diagnosed as typhoid fever. Close contact with animals and consumption of unpasteurized milk products were associated with brucellosis. The high incidence of brucellosis in Fayoum highlights its public health importance, and the need to implement prevention strategies in humans and animals.

Summary Background To investigate the risk factors for infection with endemic typhoid fever in the Samarkand region of Uzbekistan. Methods Case–control study of culture-confirmed bloodstream infection with Salmonella Typhi. Patients were compared to age-matched community controls. Salmonella Typhi isolates were tested for antimicrobial susceptibility. Results We enrolled 97 patients and 192 controls. The median age of patients was 19 years. In a conditional regression model, consumption of unboiled surface water outside the home [adjusted odds ratio (aOR) = 3.0, 95% confidence interval (CI) = 1.1–8.2], use of antimicrobials in the 2 weeks preceding onset of symptoms (aOR = 12.2, 95% CI 4.0–37.0), and being a student (aOR = 4.0, 95% CI 1.4–11.3) were independently associated with typhoid fever. Routinely washing vegetables (aOR 0.06, 95% CI 0.02–0.2) and dining at a tea-house (aOR 0.4, 95% CI 0.2–1.0) were associated with protection against illness. Salmonella Typhi resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole was identified in 6 (15%) of 41 isolates tested. Conclusions Endemic typhoid fever in Uzbekistan is transmitted by contaminated water. Recent use of antimicrobials also increased risk of infection. Targeted efforts at improving drinking water quality, especially for students and young adults, are likely to decrease transmission of typhoid fever. Measures to decrease the unnecessary use of antimicrobials would be expected to reduce the risk of typhoid fever and decrease the spread of multiple drug-resistant Salmonella Typhi. Donnees de base Investiguer les facteurs de risque pour l'infection a la fievre typhoide endemique dans la region de Samarkand en Ouzbekistan. Methodes etude cas-temoins de l'infection de la circulation sanguine par Salmonella Typhi, confirmee par la culture. Les patients ont ete compares a des temoins d’âge comparable dans la communaute. Le test de sensibilite aux antimicrobiens a ete realise sur les isolats disponibles de Salmonella Typhi. Resultats Nous avons recrute 97 patients et 192 temoins. L’âge median des patients etait de 19 ans. Dans un modele de regression conditionnelle, la consommation d'eau de surface non bouillie hors de la maison [rapport de cotes ajuste (aOR) = 3,0; intervalle de confiance a 95% (IC95%): 1,1–8,2], l'utilisation d'antimicrobiens dans les deux semaines precedant le debut des symptomes (aOR = 12,2; IC95%: 4,0–37,0) et le fait d’etre etudiant (aOR = 4,0; IC95%: 1,4–11,3) etaient independamment associes a la fievre typhoide. Le lavage regulier des legumes (aOR = 0,06; IC95%: 0,02–0,2) et le fait de diner dans un salon de the (aOR = 0,4; IC95%: 0,2–1,0) etaient associes a la protection contre la maladie. Des souches de Salmonella Typhi resistantes a l'ampicilline, au chloramphenicol et au trimethoprime-sulfamethoxazole ont ete identifiees chez 6 (15%) des 41 isolats examines. Conclusions La fievre typhoide endemique en Ouzbekistan est transmise par l'eau souillee. L'utilisation recente des antimicrobiens a egalement augmente le risque d'infection. Les efforts vises a ameliorer la qualite de l'eau potable, particulierement pour les etudiants et les jeunes adultes, sont susceptibles de diminuer la transmission de la fievre typhoide. Des mesures pour la reduction de l'utilisation non necessaire des antimicrobiens devraient reduire le risque de fievre typhoide et la propagation de souches MDR de Salmonella Typhi. Antecedentes Investigar los factores de riesgo para infeccion con fiebre tifoidea endemica en la region de Samarkand de Uzbekistan. Metodos Estudio caso-control de infeccion sanguinea por Salmonella Typhi, confirmada mediante cultivo. Se comparo a los pacientes vs. controles comunitarios, apareados por edad. La susceptibilidad a antimicrobianos se determino sobre aislados disponibles de Salmonella Typhi. Resultados Se incluyeron 97 pacientes y 192 controles. La edad media de los pacientes era 19 anos. En un modelo de regresion condicional, el consumo de agua superficial, fuera de casa, sin hervir [odds ratio ajustado (ORa) = 3.0, 95% intervalo de confianza (IC) = 1.1–8.2], el uso de antimicrobianos en las dos semanas anteriores al comienzo de los sintomas (aOR = 12.2, 95% IC 4.0–37.0), y el ser estudiante (ORa = 4.0, 95% IC 1.4–11.3), estaban independientemente asociadas a la fiebre tifoidea. El lavado rutinario de los vegetales (ORa 0.06, 95% IC 0.02–0.2) y el cenar en una casa de te (ORa 0.4, 95% IC 0.2–1.0) estaban asociadas a proteccion frente a la enfermedad. Se identifico resistencia a ampicilina, cloranfenicol, y trimetoprim/sulfametoxazol en 6 (15%) de los 41 aislados de Salmonella Typhi testados. Conclusiones La fiebre tifoidea endemica en Uzbekistan se transmite mediante agua contaminada. El uso reciente de antimicrobianos ha aumentado el riesgo de infeccion. Esfuerzos dirigidos a mejorar la calidad del agua potable, especialmente para estudiantes y jovenes adultos, podria disminuir la transmision de fiebre tifoidea. Se esperaria tambien que el tomar medidas para disminuir el uso innecesario de antimicrobianos redujese el riesgo de fiebre tifoidea y disminuyese la propagacion de cepas Salmonella Typhi multirresistentes.

With the expansion and convergence of the HIV and TB epidemics worldwide, clinicians will increasingly will be called to manage and treat co-infected patients. TB and HIV medications have overlapping and additive toxicities that can complicate therapy. Additional clinical challenges include choice of optimal first and second line antiretroviral therapy, appropriate timing of antiretroviral initiation, management of immune reconstitution disease, and TB diagnosed after initiation of HIV therapy. Despite the complexities presented by co-infection, many programmes have integrated care and are successfully treating patients with both HIV and TB.

Credible measures of disease incidence are necessary to guide typhoid fever control efforts. In Egypt, incidence estimates have been derived from hospital-based syndromic surveillance, which may not represent the population with typhoid fever. To determine the population-based incidence of typhoid fever in Fayoum Governorate (pop. 2,240,000), we established laboratory-based surveillance at five tiers of health care. Incidence estimates were adjusted for sampling and test sensitivity. Of 1,815 patients evaluated, cultures yielded 90 (5%) Salmonella Typhi isolates. The estimated incidence of typhoid fever was 59/100,000 persons/year. We estimate 71% of typhoid fever patients are managed by primary care providers. Multidrug-resistant (MDR) Salmonella Typhi (resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) was isolated from 26 (29%) patients. Population-based surveillance indicates moderate typhoid fever incidence in Fayoum, and a concerning prevalence of MDR typhoid. The majority of patients are evaluated at the primary care level and would not have been detected by hospital-based surveillance.

We compared the clinical features of 8 U.S. case-patients with laboratory-confirmed severe acute respiratory syndrome (SARS) to 65 controls who tested negative for SARS coronavirus (SARS-CoV) infection. Shortness of breath, vomiting, diarrhea, progressive bilateral infiltrates on chest radiograph, and need for supplemental oxygen were significantly associated with confirmed SARS-CoV infection.

Salmonella Javiana is a Salmonella serotype that is restricted geographically in the United States to the Southeast. During the summer of 2001, the number of reported S. Javiana infections in Mississippi increased sevenfold. To identify sources of infection, we conducted a case-control study, defining a case as an infection with S. Javiana between August and September in a Mississippi resident. We enrolled 55 cases and 109 controls. Thirty (55%) case patients reported exposure to amphibians, defined as owning, touching, or seeing an amphibian on one's property, compared with 30 (29%) controls (matched odds ratio 2·8, P=0·006). Contact with amphibians and their environments may be a risk factor for human infection with S. Javiana. The geographic pattern of S. Javiana infections in the United States mimics the distribution of certain amphibian species in the Southeast. Public health officials should consider amphibians as potential sources of salmonellosis, and promote hand washing after contact with amphibians.

This letter to the editor centers on low-level viremia among Ugandan adults infected with HIV and with untreated active tuberculosis. It suggests further investigation into the relative contribution of macrophage infection T-cell activation stimulating inhibitory cytokines viral tropism and viral subtype to better understand the potential causes of low-level HIV viremia with active TB.

In 2010, 3.5 million people were living with HIV in the World Health Organization Southeast Asia Region (SEAR), giving this region the greatest burden of HIV after Africa. Scale-up of antiretroviral therapy has resulted in over 717,000 benefitting from it by the end of 2010. A systematic review of studies of HIV drug resistance in the SEAR published between 2000 and 2011 was performed. Of 10 studies of transmitted HIV drug resistance in recently infected patients, all but two reported low levels (5%) of transmitted resistance. Of 23 studies of HIV drug resistance in pretreatment populations initiating antiretroviral therapy, three reported moderate levels (5-15%) of HIV drug resistance and 20 reported low levels. Amongst 17 studies of acquired HIV drug resistance, levels of nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor resistance ranged from 52 to 92% and 43 to 100%, respectively, amongst those with virological failure. Overall, data included in this review suggest that currently recommended first- and second-line regimens are appropriate for the cohorts studied. However, data were only available from two of 11 Southeast Asia Region countries and studies largely examined urban populations. Results are unlikely to be representative of the region. Studies lacked standardized methods, which greatly limits comparability of data and their use for public health and antiretroviral therapy program planning. Routine, standardized, and nationally representative HIV drug resistance surveillance should be strongly encouraged in the Southeast Asia Region countries to best characterize population-level HIV drug resistance. National-level HIV drug resistance surveillance data may be used to optimize delivery of HIV care and treatment and minimize emergence of population-level HIV drug resistance, thus promoting the long-term efficacy and durability of available first- and second-line antiretroviral therapy regimens.

Surveillance for transmitted HIV drug resistance is essential to assessing the longer term sustainability and durability of first-line antiretroviral therapy (ART). Increases in pre-ART resistance would compromise the ability to achieve optimal and durable treatment outcomes using currently recommended antiretrovirals.In the Asia region, many countries have conducted studies of transmitted resistance among recently HIV-infected and pre-ART patients. Data vary by methodology and resistance interpretation systems. Studies in some high-income settings have shown stabilizing or declining rates (e.g. Taiwan, Hong Kong), and increasing rates in others (e.g. Japan). In low-income and middle-income Asian countries, resistance has primarily been reported to be below WHO thresholds for moderate resistance (i.e.5%). However, studies have identified an increased risk of resistance associated with male-to-male sex and/or higher rates among cohorts of MSM. Some countries still lack systematically collected transmitted resistance data.To date, there does not appear to be a need for baseline resistance testing in most Asian settings for which there are data. However, MSM appear to be at higher risk of transmitted resistance and may benefit from enhanced resistance assessments and prevention interventions.

Background The identification and management of first-line antiretroviral therapy (ART) failure is a key challenge for HIV programs in resource-limited settings. In 2008, the National AIDS Control Organisation, India piloted a national strategy to provide second-line ART. We assessed the National AIDS Control Organisation second-line ART evaluation algorithm. Methods Adult patients who had received 6 months or more of standard first-line ART were referred for second-line ART evaluation if they demonstrated CD4 decline to pre-ART values, CD4 drop to less than 50% of peak on-treatment value, failure to achieve CD4 greater than 100 c/mm(3), or development of a new World Health Organization Stage 3 or 4 AIDS-defining illness. Patients received HIV RNA testing, and those with HIV RNA 10,000 c/mL or greater qualified to switch to second-line ART. World Health Organization-defined clinical and CD4 criteria for ART failure were compared against virologic failure criteria. Results Between January and June 2008, 154 patients met criteria for evaluation. Of 122 (79%) patients who had HIV RNA testing, 87 (71%) had viral load 10,000 c/mL or greater and were recommended to start second-line ART, 29 (24%) had viral load less than 400 c/mL, and six (5%) had viral load between 400 and 10,000 c/mL. The positive predictive value of World Health Organization clinical/immunologic criteria to detect virologic failure was 71% (95% confidence interval, 63% to 79%). Conclusions Second-line ART was initiated in the public sector in India using an approach combining clinical and immunologic evaluation with confirmation of virologic failure. Almost 25% of patients who met clinical/immunologic failure criteria demonstrated virologic suppression. Inclusion of targeted HIV RNA testing in the evaluation of treatment failure can prevent unnecessary switches to second-line ART.

A survey for transmitted HIV drug resistance (HIVDR) was conducted according to WHO guidelines among clients newly diagnosed with HIV-1 infection at two voluntary counseling and testing centers (VCTC) in Mumbai. HIVDR testing was performed using the ViroSeq RT-PCR method (Abbott). Out of 50 successfully amplified and sequenced specimens, analysis of the first 34 consecutively collected specimens revealed no nucleoside reverse transcriptase inhibitor, nonnucleoside reverse transcriptase inhibitor, or protease inhibitor mutations from the 2007 WHO list of mutations for surveillance of transmitted HIVDR, indicating that the prevalence of transmitted HIVDR to all three drug classes was

Background Nucleic acid amplification tests are sensitive and specific for identifying Mycobacterium tuberculosis in sputum smear-positive populations, but they are less sensitive in sputum smear-negative populations. Few studies have assessed their performance among patients infected with HIV, and no studies have assessed their performance with oral wash specimens, which may be easier to obtain than sputum samples. Methods We performed a prospective study involving 127 adults from 2 populations who were undergoing evaluation for respiratory complaints at Mulago Hospital in Kampala, Uganda. We obtained and tested sputum samples for Mycobacterium tuberculosis, and we simultaneously obtained oral wash specimens to test for M. tuberculosis DNA by polymerase chain reaction (PCR) amplification of a novel locus, the secA1 gene. A positive mycobacterial culture of sputum was used to define cases of tuberculosis; we calculated the sensitivity and specificity of the PCR assay with sputum or oral wash specimens in reference to the standard of sputum culture results. Results Tuberculosis (75 [59%] of 127 patients) and HIV infection (58 [46%] of 126 patients) were both common in the study population. PCR of sputum samples was highly sensitive (sensitivity, 99%; 95% confidence interval, 93%-100%) and specific (specificity, 88%; 95% confidence interval, 77%-96%) for detection of pulmonary tuberculosis and performed well among HIV-infected patients and among patients with negative sputum smear results. PCR of oral wash specimens was less sensitive (sensitivity, 73%; 95% confidence interval, 62%-83%) but also detected a substantial proportion of tuberculosis cases. Conclusions PCR targeting the secA1 gene was highly sensitive and specific for identifying M. tuberculosis in sputum samples, independent of smear or HIV infection status. Oral washes showed promise as an easily obtained respiratory specimen for tuberculosis diagnosis. PCR of sputum for detection of the secA1 gene could be a rapid, effective diagnostic tool for tuberculosis referral centers.

Triple nucleoside reverse transcriptase inhibitors are recommended as an alternative regimen for HIV-infected patients undergoing tuberculosis treatment in resource-limited settings. Few data exist on the efficacy of such regimens in tuberculosis patients. In 34 tuberculosis/HIV-co-infected patients treated with zidovudine/lamivudine/abacavir 76% achieved HIV RNA less than 50 copies/ ml at 24 weeks. No cases of hypersensitivity or immune reconstitution syndrome were observed. These data support the continuing evaluation of nucleoside-based antiretroviral regimens as an alternative treatment for this population. (authors)

To investigate the risk factors for infection with endemic typhoid fever in the Samarkand region of Uzbekistan.Case-control study of culture-confirmed bloodstream infection with Salmonella Typhi. Patients were compared to age-matched community controls. Salmonella Typhi isolates were tested for antimicrobial susceptibility.We enrolled 97 patients and 192 controls. The median age of patients was 19 years. In a conditional regression model, consumption of unboiled surface water outside the home [adjusted odds ratio (aOR)=3.0, 95% confidence interval (CI)=1.1-8.2], use of antimicrobials in the 2 weeks preceding onset of symptoms (aOR=12.2, 95% CI 4.0-37.0), and being a student (aOR=4.0, 95% CI 1.4-11.3) were independently associated with typhoid fever. Routinely washing vegetables (aOR 0.06, 95% CI 0.02-0.2) and dining at a tea-house (aOR 0.4, 95% CI 0.2-1.0) were associated with protection against illness. Salmonella Typhi resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole was identified in 6 (15%) of 41 isolates tested.Endemic typhoid fever in Uzbekistan is transmitted by contaminated water. Recent use of antimicrobials also increased risk of infection. Targeted efforts at improving drinking water quality, especially for students and young adults, are likely to decrease transmission of typhoid fever. Measures to decrease the unnecessary use of antimicrobials would be expected to reduce the risk of typhoid fever and decrease the spread of multiple drug-resistant Salmonella Typhi.

Credible measures of disease incidence are necessary to guide typhoid fever control efforts. In Egypt, incidence estimates have been derived from hospital-based syndromic surveillance, which may not represent the population with typhoid fever. To determine the population-based incidence of typhoid fever in Fayoum Governorate (pop. 2,240,000), we established laboratory-based surveillance at five tiers of health care. Incidence estimates were adjusted for sampling and test sensitivity. Of 1,815 patients evaluated, cultures yielded 90 (5%) Salmonella Typhi isolates. The estimated incidence of typhoid fever was 59/100,000 persons/year. We estimate 71% of typhoid fever patients are managed by primary care providers. Multidrug-resistant (MDR) Salmonella Typhi (resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) was isolated from 26 (29%) patients. Population-based surveillance indicates moderate typhoid fever incidence in Fayoum, and a concerning prevalence of MDR typhoid. The majority of patients are evaluated at the primary care level and would not have been detected by hospital-based surveillance.

We investigated a large outbreak of Salmonella enterica serotype Javiana among attendees of the 2002 U.S. Transplant Games, including 1,500 organ transplant recipients. Web-based survey methods identified pre-diced tomatoes as the source of this outbreak, which highlights the utility of such investigative tools to cope with the changing epidemiology of foodborne diseases.