Micro-organisms and risk factors associated with prosthetic joint infection following primary total knee replacement-our experience in Pakistan.

PURPOSE: To identify potential risk factors and micro-organisms associated with prosthetic joint infection following primary total knee replacement surgery. HYPOTHESIS OF STUDY: Our hypothesis is that body mass index (BMI), operative time, type of surgery, and order of surgery especially in bilateral simultaneous cases have a major impact on prosthetic joint infection (PJI). METHODOLOGY: We identified 4269 patients who underwent for primary knee replacement surgery between 2008 and 2018. We recorded patient demographics, comorbidities, order of surgery, type of surgery, causative micro-organism, and their antibiotic susceptibility. Multivariable logistic regression analysis was built to identify risk factors that are associated with prosthetic joint infection following primary total knee replacement. RESULTS: Forty-eight patients developed prosthetic joint infection. The factors that are found to be associated with prosthetic joint infection are BMI, operative time, type of surgery, order of surgery, diabetes, and rheumatoid arthritis. Methicillin-resistant Staphylococcus aureus (MRSA) was the major underlying pathogen seen in majority of cases. CONCLUSION: Despite low incidence of prosthetic joint infection following primary total knee replacement, there are patients at higher risk that would benefit by addressing modifying risk factors significantly associated with prosthetic joint infection.

Risk Factors of Crimean-Congo Haemorrhagic Fever in Sindh Province, Pakistan.

OBJECTIVES: In Sindh Province, Pakistan, confirmed Crimean-Congo haemorrhagic fever (CCHF) increased from zero in 2008 to 16 in 2015-2016. To counter this increase, in 2016, we initiated structured CCHF surveillance to improve estimates of risk factors for CCHF in Sindh and to identify potential interventions. METHODS: Beginning in 2016, all referral hospitals in Sindh reported all CCHF cases to surveillance agents. We used laboratory-confirmed cases from CCHF surveillance from 2016 to 2020 to compute incidence rates and in a case-control study to quantify risk factors for CCHF. RESULTS: For the 5 years, CCHF incidence was 4.2 per million for the Sindh capital, Karachi, (68 cases) and 0.4 per million elsewhere. Each year, the onset of new cases peaked during the 13 days during and after the 3-day Eid-al-Adha festival, when Muslims sacrificed livestock, accounting for 38% of cases. In Karachi, livestock for Eid were purchased at a seasonal livestock market that concentrated up to 700,000 livestock. CCHF cases were most common (44%) among the general population that had visited livestock markets (odds ratio = 102). CONCLUSIONS: Urban CCHF in Sindh province is associated with the general public's exposure to livestock markets in addition to high-risk occupations.

A pediatric HIV outbreak in Pakistan.

Background: Following reports of an outbreak of HIV infection among children in Larkana District, Pakistan, an international team investigated the extent and cause of the outbreak between April and June 2019. Aims: To investigate the incidence of HIV among children in Larkana District, Pakistan and describe the distribution of cases by time, place and person. Methods: Self-referred persons were tested for HIV using the national testing protocol. Local epidemiology of HIV was reviewed to generate hypotheses. An infection prevention and control (IPC) team conducted site visits and reviewed IPC practices. Results: Between 25 April and 27 June 2019, a total of 30 191 persons were tested for HIV in Larkana District, and 876 of them tested positive. Of those who tested positive, 719 (82%) were children aged <15 years. Traditional skin piercing procedures and transmission from high-risk populations to children were ruled out during the investigation. Informative interviews with parents or guardians of a convenience sample of 211 children aged <15 years showed that 99% of children had an injection or infusion for medical treatment within the past 12 months. Our investigation identified lack of HIV prevalence data for the general population including tuberculosis patients and those who attended antenatal care services. Conclusions: Investigations indicate that unsafe healthcare practices in formal and informal healthcare settings as the most likely cause of the 2019 outbreak of HIV infection in Larkana, Pakistan. Measures should be taken to improve IPC practices at the facility level, especially in pediatric and antenatal care clinics.

An Epidemic of Pediatric HIV From Reuse of Infusion Equipment in Pakistan.

BACKGROUND: From April to June 2019, a total of 909 new HIV infections were identified in Larkana, Pakistan; 86% was children younger than 15 years. To identify the possible transmission links in this outbreak, a case-control study was conducted in June 2019. METHODS: For cases, we selected a systematic random sample of 100 HIV-positive children from the screening list. We chose 2 age-matched and sex-matched controls from the neighborhood of each HIV-positive case. All selected children were tested using the World Health Organization-approved rapid diagnosis test algorithm. We interviewed the parents of each selected child about previous exposures to parenteral treatment and compared exposures of case and control children using conditional logistic regression. RESULTS: The ages of the selected children ranged from 1 month to 10 years. More than 90% of both HIV+ and HIV- children had received outpatient health care from MBBS-qualified private physicians. Eighty-three percent of HIV+ children versus 46% of HIV- children had received health care from one private physician [adjusted odds ratio (aOR) = 29, 95% confidence interval (95% CI): 10 to 79]. Intravenous infusions during the last outpatient visit were reported by 29% of case versus 7% of controls (aOR 57, 95% CI: 2.9 to >1000), whereas no case children and 17% of control children had received only intramuscular injections (aOR 0, 95% CI: 0 to 41). Among cases, 94% had been given infusions through a drip set compared with 85% of control children (aOR = 7.7, 95% CI: 2.3 to 26). Infusions had been administered with reused IV drip sets in 70% of cases compared with 8% of controls (aOR = 197, 95% CI: 16 to 2400). DISCUSSION: Private physicians reusing intravenous drip sets to treat outpatients seen in private practice were responsible for this HIV epidemic. Mapping and regulation of private practitioners were suggested.

The Relationship of Drug Therapy to Aplastic Anemia in Pakistan: A Hospital-Based Case Control Study.

INTRODUCTION: Drug-induced aplastic anemia has long been a menacing outcome of modern pharmacotherapy. The incidence of idiosyncratic, drug-induced aplastic anemia varies depending on the genetic susceptibility and the associated drug. Only scarce studies have explained the epidemiology and actual incidence of this reaction. PURPOSE: The aim of the study was to establish the association between drugs and aplastic anemia. METHODS: A case-control study was conducted with 191 cases and 696 controls at a tertiary hospital for blood diseases in Karachi-Pakistan. Cases were patients of aplastic anemia diagnosed through bone marrow biopsy. The controls did not have either AA or chronic diseases. Each case was paired with four sex and age group match controls. Cases and controls were compared with respect to the drugs used. Univariate and multivariate analysis were performed in order to delineate the association. RESULTS: Median age of the study-participants was 27 years (04-69 years). The majority 84 (44%) were from age group 16 to 30 years. The male-to-female ratio was 2:1. Among study participants, various drugs were significantly associated with aplastic anemia. Treatment of epilepsy with carbamazepine showed a positive association (OR=2.7, 95% C.I, 1.0-6.8). An increased risk of aplastic anemia was noted with exposure to thiazide (OR=3.1, 95% C.I, 1.3-7.4) and mebendazole (OR=3.7, 95% C.I, 1.5-9.2). However, risks were not increased with chloramphenicol, trimethoprim/sulfamethoxazole, benzodiazepines, antihistamines, oral contraceptives, and herbal medicine. CONCLUSION: This large-scale case-control study provide association of aplastic anemia with exposure to carbamazepine, thiazides and mebendazole in population of Pakistan. Patients should be monitored with complete blood indices for early detection of drug toxicity.

Impact of Tibial Tubercle Osteotomy on Final Outcome in Revision Total Knee Arthroplasty: Our Experience and Technique in Pakistan.

BACKGROUD: Due to extensive fibrosis during revision surgery, adequate exposure is essential and it can be achieved with several extensile approach options, such as tibial tubercle osteotomy. Information regarding surgical exposure during revision arthroplasty is limited in developing countries, such as Pakistan, due to the lack of adequate data collection and follow-up. Therefore, the purpose of this study was to evaluate the impact of tibial tubercle osteotomy on final outcome of revision total knee arthroplasty (TKA). METHODS: A total of 231 revision TKAs were performed between January 2008 and December 2017. Twenty-nine patients underwent tibial tubercle osteotomy for adequate exposure during revision surgery. Of these, 27 patients with complete follow-up were included in our study. Factors examined include age at the time of revision surgery, gender, comorbidities, arthroplasty site (right or left), body mass index (BMI), and primary indications for the tibial tubercle osteotomy during revision TKA. Functional outcome was measured by using Knee Society score (KSS) at 3 months and the final follow-up. All statistical analysis was done using SPSS version 20.0 with a p-value < 0.05 considered significant. RESULTS: Out of 27 patients, 6 patients (22.2%) were men and 21 patients (77.7%) were women. Right knee revision arthroplasty was performed in 15 patients (55.5%), left knee revision arthroplasty was performed in 12 patients (44.4%), and bilateral revision surgery was performed in only 1 patient (3.7%). The mean BMI was 29.2 kg/m2. We used a constrained condylar knee in 20 patients (74%), a rotating hinge knee in 5 patients (18.5%), and mobile bearing tray plus metaphyseal sleeves in 2 patients (7.4%). The KSS was 52.21 ± 4.05 preoperatively, and 79.42 ± 2.2 and 80.12 ± 1.33 at 3 months and 12 months, respectively. Radiological union was achieved in all patients at 3 months. Of 27 patients, only 1 patient (3.7%) had proximal migration of the osteotomy site at 6 months: the patient was asymptomatic and union was also achieved and, therefore, no surgical intervention was performed. CONCLUSIONS: Tibial tubercle osteotomy during revision TKA can be a safe and reliable technique with superior outcomes and minimal complication rates.

Morbidity and Mortality Associated with Typhoid Fever Among Hospitalized Patients in Hyderabad District, Pakistan, 2017-2018: Retrospective Record Review.

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.

Effectiveness of typhoid conjugate vaccine against culture-confirmed Salmonella enterica serotype Typhi in an extensively drug-resistant outbreak setting of Hyderabad, Pakistan: a cohort study.

BACKGROUND: Salmonella enterica serotype Typhi (S Typhi) is a major public health problem in low-income and middle-income 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. METHODS: This 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, culture-confirmed 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 culture-confirmed 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.

Economic Burden of Periprosthetic Joint Infection Following Primary Total Knee Replacement in a Developing Country.

BACKGROUND: Periprosthetic joint infection is one of the devastating complications after primary total knee arthroplasty, which increases the financial burden on patients and affects their quality of life as well. The financial burden of periprosthetic joint infection after joint replacement in developed countries is well known. There is a need to evaluate the economic burden in developing countries such as Pakistan. METHODS: This is a single-center, retrospective, case-control study conducted at the Department of Orthopedic Surgery, Liaquat National Hospital Karachi. Cases of primary total knee arthroplasty performed during this study were divided into 2 groups: uneventful primary total knee arthroplasty and periprosthetic joint infection treated with 2-stage revision. To calculate the final cost, we divided the total hospital cost into the hospital stay cost and operating room cost. RESULTS: During study period, 32 patients were diagnosed with periprosthetic joint infection. The total cost of revision surgery for periprosthetic joint infection considering 2 hospitalizations was 1,780,222 ± 313,686 Pakistani rupee (PKR). The total cost of uneventful arthroplasty was 390,172 ± 51,460 PKR. We observed significant difference with respect to economic details between the 2 groups. CONCLUSIONS: Management of periprosthetic joint infection was 4.5 times more expensive than uneventful primary total knee arthroplasty. Measures should be undertaken to reduce the prevalence of periprosthetic joint infection, thereby reducing patients' economic burden.

Outbreak investigation of ceftriaxone-resistant Salmonella enterica serotype Typhi and its risk factors among the general population in Hyderabad, Pakistan: a matched case-control study.

BACKGROUND: Pakistan is currently facing the largest outbreak of ceftriaxone-resistant Salmonella enterica serotype Typhi described to date. Here we aimed to report the outbreak investigation done in Hyderabad, Pakistan, and identify disease risk factors. METHODS: We did an age-matched case-control (1:4) study, in which cases of ceftriaxone-resistant S Typhi were identified from active sentinal sites (three hospitals in Hyderabad, Pakistan), community, and laboratory-based surveillance. Ceftriaxone-resistant S Typhi infection (ie, resistance to ampicillin, chloramphenicol, co-trimoxazole, fluoroquinole, and ceftriaxone) was confirmed using blood culture. Healthy participants (controls) were enrolled for the first 200 people (cases) with ceftriaxone-resistant S Typhi. A structured questionnaire was administered to identify exposures 4 weeks before the illness (cases) or enrolment (controls). Cases were included if written informed consent was provided. Four controls were selected from the same community as the corresponding case, matched on age, being healthy at the time of enrolment, and with no febrile illness in the 4 weeks before enrolment. Samples of drinking water from households and community water sources (ie, hand pumps or taps in common areas outside households) were collected for testing. Conditional logistic regression analysis was used to assess the risk factors for ceftriaxone-resistant S Typhi outbreak in Hyderabad. FINDINGS: Between Nov 30, 2016, and Dec 30, 2017, 486 people with ceftriaxone-resistant S Typhi were identified from Hyderabad. Of the 486 cases, 296 (61%) were male and 447 (92%) were aged 15 years or younger. Several factors were significantly associated with acquisition of ceftriaxone-resistant S Typhi, including male sex (adjusted odds ratio [aOR] 1·53, 95% CI 1·06-2·21), eating outside of the house (aOR 1·48, 1·01-2·19), exposure to a patient with S Typhi infection (aOR 3·81, 2·21-6·83), and a history of antimicrobial use (aOR 4·25, 2·53-7·13). Nine (69%) of 13 water samples taken from the households of people with ceftriaxone-resistant S Typhi infection were positive for Escherichia coli, indicating faecal contamination. S Typhi DNA was detected in 12 (22%) of 55 water samples from community water sources. Geospatial mapping showed clustering of cases around sewerage lines. INTERPRETATION: Hyderabad faces the largest reported outbreak of ceftriaxone-resistant S Typhi. The outbreak is suspected to be attributed to the contaminated drinking water, especially the mixing of sewage with drinking water. The risk of ceftriaxone-resistant S Typhi infection is increased among children aged 15 years and younger, male individuals, and those eating outside the house. Vaccination and chlorination of water are recommended for the containment of the outbreak. FUNDING: None.