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BackgroundThe Aga Khan University clinical microbiology laboratory identified an outbreak of ceftriaxone-resistant Salmonella Typhi in Hyderabad, Pakistan, through antimicrobial resistance surveillance. An outbreak investigation was carried out to identify the risk factors and institute control measures. Here we report the preliminary findings of this outbreak investigation, using data collected from 30 November 2016 to 28 March 2017.MethodsThe design for the investigation was a case-control study that included identification of culture-proven ceftriaxone-resistant S. Typhi cases, suspected cases from the households or neighborhood of the confirmed cases, and enrollment of controls matched by age to identify the risk factors. Data were collected through face-to-face interviews using a structured questionnaire. Blood cultures were obtained from all suspected cases. Drinking water samples from each household of cases and controls were obtained for microbiological testing. Geographic Information System coordinates were obtained for all cases and controls.ResultsOnly 2 subdistricts of Hyderabad (Latifabad and Qasimabad) were affected. A total of 101 confirmed cases of ceftriaxone-resistant S. Typhi had been reported in 4 months with the first case reported on 30 November 2016. Median age was 48 (interquartile range, 29–84) months. The majority (60% [61/101]) of the cases were 6–60 months old. More than half (56% [57/101]) of the cases were male. About 60% of the cases were admitted to hospital and treated as inpatient. More than half (57/101) of the patients developed complications related to typhoid.ConclusionsCommunity awareness was raised regarding chlorination of drinking water and sanitation measures in Hyderabad. These efforts were coordinated with the municipal water and sewage authority established to improve chlorination at processing plants and operationalize fecal sludge treatment plants. Outbreak investigation and control efforts have continued. Immunization of children with typhoid conjugate vaccine within Hyderabad city is planned.

Background Salmonella enterica serotype Typhi (S Typhi) is a major public health problem in low-income and middleincome countries. We aimed to investigate the effectiveness and impact of the typhoid conjugate vaccine Typbar-TCV against S Typhi among children in an outbreak setting of extensively drug-resistant (XDR) S Typhi in Pakistan. MethodsThis cohort study was done from Feb 21, 2018, to Dec 31, 2019. A census survey of all households located in the Qasimabad and Latifabad subdistricts of Hyderabad, Pakistan, was done at baseline, and 174 005 households were registered in the census. The Typbar-TCV immunisation campaign was initiated at temporary vaccination centres and 207 000 children aged 6 months to 10 years were vaccinated from Feb 21, 2018, to Dec 31, 2018. Social mobilisers informed parents about the vaccination process. Vaccination records were maintained electronically and linked with the household census surveys. Active surveillance for suspected and blood-culture-confirmed S Typhi was established in hospitals, clinics, and laboratories to assess the following outcomes: cases of suspected typhoid fever, cultureconfirmed S Typhi, and antimicrobial resistance. An age-stratified cohort of 1100 vaccinated children was randomly selected from the vaccination registry, tested for Vi-IgG antibodies (data not reported), and followed up fortnightly (via telephone calls or household visits) until Dec 31, 2019, for ascertainment of outcomes during the study period. 20 847 vaccinated and unvaccinated children were randomly selected from the census registry as a quality control cohort and followed up from Oct 1 to Dec 31, 2019, for ascertainment of outcomes. Vaccine effectiveness against suspected, culture-confirmed, and XDR S Typhi was calculated. Findings 23 407 children from the census registry and surveillance system were included in the vaccine effectiveness analysis. 13 436 (57•4%) children were vaccinated, 12 214 (52•2%) were male, and 10 168 (43•4%) were aged 6-59 months. 5378 (23•0%) of 23 407 children had suspected S Typhi, among whom 775 (14•4%) had cultureconfirmed S Typhi and 361 (68•6%) of 526 had XDR S Typhi. Vaccine effectiveness was 55% (95% CI 52-57) against suspected S Typhi (regardless of culture confirmation), 95% (93-96) against culture-confirmed S Typhi, and 97% (95-98) against XDR S Typhi. Interpretation Typbar-TCV is effective in protecting children against S Typhi infection in an outbreak setting, and was able, with moderate deployment, to curtail a major XDR S Typhi outbreak in a densely populated setting. The vaccine shows efficacy against S Typhi irrespective of antimicrobial resistance. Funding Bill & Melinda Gates Foundation.

Background Hyderabad, Pakistan, was the first city to witness an outbreak of extensively drug resistant (XDR) typhoid fever. The outbreak strain is resistant to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, fluoroquinolones, and third-generation cephalosporin, thus greatly limiting treatment options. However, despite over 5000 documented cases, information on mortality and morbidity has been limited. Objective To address the existing knowledge gap, this study aimed to assess the morbidity and mortality associated with XDR and non-XDR Salmonella serovar Typhi infections in Pakistan. Methods We reviewed the medical records of culture-confirmed typhoid cases in 5 hospitals in Hyderabad from October 1, 2016, to September 30, 2018. We recorded data on age, gender, onset of fever, physical examination, serological and microbiological test results, treatment before and during hospitalization, duration of hospitalization, complications, and deaths. Results A total of 1452 culture-confirmed typhoid cases, including 947 (66%) XDR typhoid cases and 505 (34%) non-XDR typhoid cases, were identified. Overall, ≥1 complications were reported in 360 (38%) patients with XDR typhoid and 89 (18%) patients with non-XDR typhoid (P<.001). Ileal perforation was the most commonly reported complication in both patients with XDR typhoid (n=210, 23%) and patients with non-XDR typhoid (n=71, 14%) (P<.001). Overall, mortality was documented among 17 (1.8%) patients with XDR S Typhi infections and 3 (0.6%) patients with non-XDR S Typhi infections (P=.06). Conclusions As this first XDR typhoid outbreak continues to spread, the increased duration of illness before hospitalization and increased rate of complications have important implications for clinical care and medical costs and heighten the importance of prevention and control measures.

Introduction: COVID-19, a novel disease, appeared in December 2019 in China and rapidly spread across the world. Till the second week of April 2020, high incidence (2.9/100,000) and cases fatality rates (1.7%) were observed in Pakistan. This study was conducted to determine the temporal and spatial distribution of the first 100 deaths attributed to COVID-19 in Pakistan and their associated demographic factors. Method: A record review of the first 100 deaths reported among RT-PCR confirmed COVID-19 cases was conducted. Demographic, epidemiological, and risk factors information was obtained associated comorbidities and clinical signs and symptoms were recorded and frequencies were determined. Results: A total of 100 mortalities with an overall case fatality rate of 1.67% (CFR) were analyzed. The median age of patients was 64.5 years (IQR: 54-70) with 75% (n=75) males. Among all deaths reported, 71 (71%) cases had one or more documented comorbidities at the time of diagnosis.  The most frequently reported co-morbidities were: hypertension (67%), followed by Diabetes Mellitus (45%) and Ischemic Heart Diseases (27%). The most frequent presenting symptoms were shortness of breath (87%) and fever (79%). The median duration of illness was eight days (IQR: 4-11 days), the median delay reaching hospital to seek health care was three days (IQR: 0-6 days) while the median duration of hospital stay was also three days (IQR: 1-7 days). Among all, 62% had no history of international travel. The most affected age group was 60-69 years while no death reported in the age group below 20 years.