Trends in typhoid fever during the COVID-19 pandemic in Pakistan.

INTRODUCTION: Pakistan has been experiencing an extensively drug-resistant (XDR) outbreak of typhoid for some years. We sought to evaluate how the COVID-19 pandemic impacted typhoid epidemiology in Pakistan, from the beginning of the pandemic in 2020 through the end of 2022, and the reduction of COVID-19 cases. METHODOLOGY: We compared national public COVID-19 data with retrospectively obtained patient data of confirmed S. Typhi isolates between January 2019 and December 2022 from Shaukat Khanum Memorial Cancer Hospital and Research Centre and the hospital's extended network of laboratory collection centers across Pakistan. RESULTS: We observed that during the early onset of the COVID-19 pandemic and COVID-19 peaks, typhoid positivity generally decreased. This suggests that restrictions and non-pharmaceutical interventions that limited social interactions and promoted good sanitation and hygiene practices had a positive secondary effect on typhoid. This led to an overall yearly decrease in typhoid positivity between 2019 to 2021. However, the percentage of S. Typhi cases isolated that were ceftriaxone-resistant continued to increase, suggesting the continued dominance of XDR typhoid in Pakistan. In 2022, with the alleviation of pandemic restrictions, we observed increased typhoid positivity and COVID-19 and typhoid positivity started to follow similar trends. CONCLUSIONS: Given the continued presence of COVID-19 along with XDR typhoid in Pakistan, it will be imperative to use differential testing to ensure that the epidemiology of each reported is accurate, the spread of each it contained, and that antibiotics are not misused. The use of approved vaccinations will lessen the burden of both diseases.

COVID-19 in Pakistan: A national analysis of five pandemic waves.

OBJECTIVES: The COVID-19 pandemic showed distinct waves where cases ebbed and flowed. While each country had slight, nuanced differences, lessons from each wave with country-specific details provides important lessons for prevention, understanding medical outcomes and the role of vaccines. This paper compares key characteristics from the five different COVID-19 waves in Pakistan. METHODS: Data was sourced from daily national situation reports (Sitreps) prepared by the National Emergency Operations Centre (NEOC) in Islamabad. We use specific criteria to define COVID-19 waves. The start of each COVID-19 wave is marked by the day of the lowest number of daily cases preceding a sustained increase, while the end is the day with the lowest number of cases following a 7-days decline, which should be lower than the 7 days following it. Key variables such as COVID-19 tests, cases, and deaths with their rates of change to the peak and then to the trough are used to draw descriptive comparisons. Additionally, a linear regression model estimates daily new COVID-19 deaths in Pakistan. RESULTS: Pakistan saw five distinct waves, each of which displayed the typical topology of a complete infectious disease epidemic. The time from wave-start to peak became progressively shorter, and from wave-peak to trough, progressively longer. Each wave appears to also be getting shorter, except for wave 4, which lasted longer than wave 3. A one percent increase in vaccinations decreased deaths by 0.38% (95% CI: -0.67, -0.08) in wave 5 and the association is statistically significant. CONCLUSION: Each wave displayed distinct characteristics that must be interpreted in the context of the level of response and the variant driving the epidemic. Key indicators suggest that COVID-19 preventive measures kept pace with the disease. Waves 1 and 2 were mainly about prevention and learning how to clinically manage patients. Vaccination started late during wave 3 and its impact on hospitalizations and deaths became visible in wave 5. The impact of highly virulent strains Alpha/B.1.1.7 and Delta/B.1.617.2 variants during wave 3 and milder but more infectious Omicron/B.1.1.529 during wave 5 are apparent.

Cancer incidence in Khyber Pakhtunkhwa, Pakistan, 2020.

BACKGROUND: To present the population-based cancer statistics for Khyber Pakhtunkhwa (KP), Pakistan, an incidence study was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) in Lahore, Pakistan, in 2023. METHODS: Records from various centres on new cancers diagnosed among residents of KP between January and December 2020 were gathered. Both active and passive methods of data collection were applied, and the information was saved in a central repository at SKMCH&RC. The incidence rates were computed by age group and sex and presented per 100,000 population. RESULTS: Among children (0-14 years), the Age-Standardised Incidence Rate (ASIR) was 4.0 in girls and 6.1 in boys, and haematologic malignancies were more prevalent; in adolescents (15-19 years), the ASIR was 7.7 in females, 9.4 in males, and bone tumours, haematologic malignancies, and neurological cancers were prominent; in adult females (> / = 20 years), the ASIR was 84.9, and cancers of the breast, digestive system, and reproductive organs were predominant; and adult males, the ASIR was 73.0, and cancers of the gastrointestinal tract, lip/oral cavity/pharynx, prostate, and Non-Hodgkin Lymphoma (NHL) were common. CONCLUSIONS: It is crucial to investigate the aetiology of these diseases at the community level because dietary elements, infectious diseases, and tobacco use all appear to be significant contributors. Prospective studies could play a key role in highlighting the factors linked to these diseases. Therefore, cancer registration must continue in conjunction with the exploration of risk factors.

A Scoping Review Of The Literature Of Research Ethics Committees And Ethics Review Framework In Pakistan: What We Know And What We Still Need To Learn.

OBJECTIVE: To map literature on research ethics committees, institutional review boards and ethics review framework in Pakistan to identify key insights during public health emergencies and normal times. Method: The systematic scoping review was conducted in April 2022, and comprised literature search on PubMed, World Health Organisation Global Index Medicus and Summons databases for articles published between January 2005 and February 2022. Information extracted included authors' names, year of publication, title, study methodology, and key insights under the heads of challenges and solutions. Due to data heterogeneity, key themes were identified and analysed. RESULTS: Of the 2,190 studies initially identified, 21(0.95%) were subjected to full-text review, and, from among them, 9(45%) were analysed in detail. There were 4 key insights identified: research ethics committees and institutional review boards in Pakistan remain unregulated as they are currently not registered or accredited by a competent national-level authority; most members of such committees are not formally trained to implement the mandate; internal and external pressures hinder independent decision-making of such committees; and other issues hindering the functionality and performance of research ethics committees and institutional review boards. CONCLUSIONS: Despite existing publications calling for urgent policy and regulatory reforms, there is a dearth of literature and minimal policy actions underlying the fact that ethics review remains a neglected area in Pakistan.

Genetic and antiretroviral drug resistance mutations analysis of reverse transcriptase and protease gene from Pakistani people living with HIV-1.

BACKGROUND: Antiretroviral therapy (ART) effectiveness is compromised by the emergence of HIV drug resistance mutations (DRM) and can lead to the failure of ART. Apart from intrinsic viral factors, non-compliance with drugs and/or the use of sub-optimum therapy can lead to the emergence of DRMs. In Pakistan HIV currently exists as a concentrated epidemic, however, ART coverage is very low, and drug adherence is poor. ART is selected assuming without baseline genotyping. Pakistan has recently seen a rise in treatment failures, but the country's actual burden of DRM is still unknown. In this study, we perform the genetic and drug resistance analysis of the pol gene from Pakistani HIV-positive ART-naïve and ART-experienced individuals. METHODS: In this study, HIV-1 pol was sequenced from 146 HIV-1 positive individuals, divided into ART-naïve (n = 37) and ART-experienced (n = 109). The sequences were also used to determine HIV-1 subtypes, the prevalence of DRM, and pol genetic variability. RESULTS: DRM analysis identified numerous DRMs against reverse transcriptase inhibitors in both ART-naïve and ART-experienced groups, including a few that are classified as rare. Additionally, the ART-experienced group showed mutations associated with resistance to protease inhibitors. Genetic analysis showed negative selection pressure in both groups, but a higher rate of evolution in the ART-naïve group. CONCLUSION: High prevalence of DRMs, especially against previous first-line treatment in ART- naïve and the accumulation of DRMs in ART-experienced groups is concerning and warrants that a more extensive DRM survey be carried out to inform first-line and second-line ART regimen recommendations.

COVID-19 vaccine hesitancy and attitudes in Pakistan: a cross-sectional phone survey of major urban cities.

BACKGROUND: COVID-19 mass vaccination is the only hopeful savior to curb the pandemic. Vaccine distribution to achieve herd immunity is hindered by hesitance and negative attitude of the public against COVID-19 vaccination. This study aims to evaluate the vaccine hesitancy and attitudes in major cities in Pakistan as well as their determinants. METHODS: A cross-sectional telephonic survey was conducted in June 2021 in major cities of Pakistan including Karachi, Lahore, Islamabad, Peshawar, and Gilgit, from unvaccinated urban population aged 18 years or older. Random Digit Dialing through multi-stage stratified random sampling was used to ensure representation of each target city and socio-economic classes. Questionnaire collected information on socio-demographics, COVID-19-related experiences, risk perception of infection, and receptivity of COVID-19 vaccination. Multivariate logistic regression analyses were performed to identify key determinants of vaccine hesitancy and acceptance. RESULTS: The prevalence of vaccinated population in this survey was 15%. Of the 2270 respondents, 65% respondents were willing to vaccinate, while only 19% were registered for vaccination. Factors significantly associated with vaccine willingness were older age (aOR: 6.48, 95% CI: 1.94-21.58), tertiary education (aOR: 2.02, 95% CI: 1.36, 3.01), being employed (aOR: 1.34, 95% CI: 1.01, 1.78), perceived risk of COVID-19 (aOR: 4.38, 95% CI: 2.70, 7.12), and higher compliance with standard operating procedures (aOR: 1.72, 95% CI: 1.26, 2.35). The most common vaccine hesitancy reasons were 'no need' (n = 284, 36%) and concerns with 'vaccine safety and side effects' (n = 251, 31%), while most reported vaccine motivation reasons were 'health safety' (n = 1029, 70%) and 'to end the pandemic' (n = 357, 24%). CONCLUSIONS: Although our study found 35% hesitancy rate of COVID-19 vaccine, there were noticeable demographic differences that suggest tailored communication strategy to address concerns held by most hesitant subpopulation. Use of mobile vaccination facilities particularly for less mobile and disadvantaged, and implementation and evaluation of social mobilization strategy should be considered to increase overall COVID-19 vaccination acceptance and coverage.

Raising the contraceptive prevalence rate to 50% by 2025 in Pakistan: an analysis of number of users and service delivery channels.

BACKGROUND: Pakistan is the fifth most populous country in the world, with a population that is growing at 2.4% annually. Despite considerable political will, including a national commitment that was endorsed by the president to raise the contraceptive prevalence rate (CPR) to 50% by 2025, it has stagnated at around 30-35%. Much of the dialogue on raising CPR is hypothetical and revolves around percentage point change rather than an actual number of women that must be served. METHODS: The Demographic and Health Survey 2017-18 (DHS 2017-18) provides information about the channels through which users receive family planning (FP) services and disaggregates this information at the provincial level. Proportions of users from each of these channels were multiplied by the Pakistan Census-2017 populations to arrive at the number of users. These users were compared with the total FP users and the number of women that had used any FP service in the past 12 months. Linear estimations of population were applied to calculate population numbers in 2025. RESULTS: The national target of 50% CPR by 2025 translates to a population of 20.02 million users. Currently, 11.26 million married women of reproductive age (MWRA) use any method, 8.22 million use a modern method and 4.94 million received this service in the past 12 months. Of these, 2.7 million did so from social marketing outlets, 0.76 million from public sector outreach through lady health workers (LHWs), 0.55 million from private sector and 0.88 million from public sector facilities. However, arriving at the CPR target means expanding annual service delivery from 4.94 to 13.7 million users. Since social marketing and LHW outreach may have become saturated, only public and private health facilities are the likely channels for such an expansion. CONCLUSIONS: We demonstrate triangulation of the survey data with the census data as a simple policy analysis tool that can help decision-makers estimate the quantum of services they must provide. Such an analysis also allows an understanding of the utilization patterns of each of these channels. In Pakistan's context, underutilization of funds and existing facilities suggests that increased funding or more providers will likely not be helpful. The policy changes that will likely be most effective include adding outreach to support existing public and private sector facilities while ensuring that procurement of commodities is prioritized.

Identification of Multiple Variant Extensively Drug-Resistant Typhoid Infections across Pakistan.

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a life-threatening bacterial infection. Recently, an outbreak of a new sublineage of extensively drug resistant (XDR) S. Typhi emerged in Pakistan in the province of Sindh. This sublineage had both a composite multidrug resistance transposon integrated on the chromosome and an acquired IncY plasmid carrying the extended spectrum beta-lactamase, blaCTX-M-15, which conferred resistance to third-generation cephalosporins. We observed previously that XDR typhoid had spread beyond the originating southern Sindh Province. Thus, we sought to determine the genetic diversity of 58 ceftriaxone-resistant S. Typhi clinical isolates by whole genome sequencing collected across Pakistan from November 2018 to December 2020 to provide insights into the molecular epidemiology of the evolving outbreak. We identify multiple novel genomic integrations of the extended spectrum beta-lactamase gene into the chromosome in S. Typhi, revealing the existence of various XDR typhoid variants circulating in the country. Notably, the integration of the IncY plasmid bearing antibiotic resistance genes may allow for subsequent plasmid acquisition by these variants, potentially leading to further plasmid-borne multidrug resistance. Our results can inform containment initiatives, help track associated outcomes and international spread, and help determine how widespread the risk is.

Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis.

High-Dose Rifampicin Regimen for Pulmonary TuberculosisThis randomized, controlled trial tested the efficacy and safety of high-dose rifampicin (1200 or 1800 mg/d) as part of the treatment regimen for pulmonary tuberculosis. Four-month high-dose rifampicin regimens had no dose-limiting side effects but failed to meet noninferiority criteria compared with the standard 6-month control regimen.

Community engagement to increase vaccine uptake: Quasi-experimental evidence from Islamabad and Rawalpindi, Pakistan.

Developing countries have been facing difficulties in reaching out to low-income and underserved communities for COVID-19 vaccination coverage. The rapidity of vaccine development caused a mistrust among certain subgroups of the population, and hence innovative approaches were taken to reach out to such populations. Using a sample of 1760 respondents in five low-income, informal localities of Islamabad and Rawalpindi, Pakistan, we evaluated a set of interventions involving community engagement by addressing demand and access barriers. We used multi-level mixed effects models to estimate average treatment effects across treatment areas. We found that our interventions increased COVID-19 vaccine willingness in two treatment areas that are furthest from city centers by 7.6% and 6.6% respectively, while vaccine uptake increased in one of the treatment areas by 17.1%, compared to the control area. Our results suggest that personalized information campaigns such as community mobilization help to increase COVID-19 vaccine willingness. Increasing uptake however, requires improving access to the vaccination services. Both information and access may be different for various communities and therefore a "one-size-fits-all" approach may need to be better localized. Such underserved and marginalized communities are better served if vaccination efforts are contextualized.

The Case of the Young Male with a Longstanding History of Dyspeptic Symptoms: Peritoneal Tuberculosis.

Portal vein thrombosis associated with peritoneal tuberculosis is an uncommon manifestation of extrapulmonary tuberculosis. We report one such case of a 33-year-old male with a one-year history of dyspepsia, having been on proton pump inhibitors all this time with temporary relief. In view of ongoing symptoms, an endoscopy was done, which at first showed duodenal ulcer. On repeat endoscopy after an interval, there was evidence of mucosa-associated lymphoid tissue (MALT) lymphoma, which prompted a host of investigations in the patient. A positron emission tomography (PET) scan revealed extensive omento-peritoneal involvement along with a hypodense lesion in the liver with interval development of portal vein thrombosis on a CT scan of the abdomen. The biopsy of the hepatic lesion showed granulomatous inflammation. Faced with a diagnostic dilemma, finally, a laparoscopic biopsy was done, which confirmed the diagnosis of peritoneal TB with portal vein thrombosis. This case highlights the importance of keeping a high index of suspicion to include tuberculosis as a differential when presented with a case such as this and to conduct appropriate investigations to establish the correct diagnosis.

Connecting SiO4 in Silicate and Silicate Chain Networks to Compute Kulli Temperature Indices.

A topological index is a numerical parameter that is derived mathematically from a graph structure. In chemical graph theory, these indices are used to quantify the chemical properties of chemical compounds. We compute the first and second temperature, hyper temperature indices, the sum connectivity temperature index, the product connectivity temperature index, the reciprocal product connectivity temperature index and the F temperature index of a molecular graph silicate network and silicate chain network. Furthermore, a QSPR study of the key topological indices is provided, and it is demonstrated that these topological indices are substantially linked with the physicochemical features of COVID-19 medicines. This theoretical method to find the temperature indices may help chemists and others in the pharmaceutical industry forecast the properties of silicate networks and silicate chain networks before trying.

A Paradigmatic Approach to Find the Valency-Based K-Banhatti and Redefined Zagreb Entropy for Niobium Oxide and a Metal-Organic Framework.

Entropy is a thermodynamic function in chemistry that reflects the randomness and disorder of molecules in a particular system or process based on the number of alternative configurations accessible to them. Distance-based entropy is used to solve a variety of difficulties in biology, chemical graph theory, organic and inorganic chemistry, and other fields. In this article, the characterization of the crystal structure of niobium oxide and a metal-organic framework is investigated. We also use the information function to compute entropies by building these structures with degree-based indices including the K-Banhatti indices, the first redefined Zagreb index, the second redefined Zagreb index, the third redefined Zagreb index, and the atom-bond sum connectivity index.

Optimal control problem arising from COVID-19 transmission model with rapid-test.

The world health organization (WHO) has declared the Coronavirus (COVID-19) a pandemic. In light of this ongoing global issue, different health and safety measure has been recommended by the WHO to ensure the proactive, comprehensive, and coordinated steps to bring back the whole world into a normal situation. This is an infectious disease and can be modeled as a system of non-linear differential equations with reaction rates which consider the rapid-test as the intervention program. Therefore, we have developed the biologically feasible region, i.e., positively invariant for the model and boundedness solution of the system. Our system becomes well-posed mathematically and epidemiologically for sensitive analysis and our analytical result shows an occurrence of a forward bifurcation when the basic reproduction number is equal to unity. Further, the local sensitivities for each model state concerning the model parameters are computed using three different techniques: non-normalizations, half-normalizations, and full normalizations. The numerical approximations have been measured by using System Biology Toolbox (SBedit) with MATLAB, and the model is analyzed graphically. Our result on the sensitivity analysis shows a potential of rapid-test for the eradication program of COVID-19. Therefore, we continue our result by reconstructing our model as an optimal control problem. Our numerical simulation shows a time-dependent rapid test intervention succeeded in suppressing the spread of COVID-19 effectively with a low cost of the intervention. Finally, we forecast three COVID-19 incidence data from China, Italy, and Pakistan. Our result suggests that Italy already shows a decreasing trend of cases, while Pakistan is getting closer to the peak of COVID-19.

In vitro Analysis of Surface Roughness Produced by an Air Polishing Device and Conventional Root Planing on Cementum: A Profilometric Study.

Context: Tooth surface polishing is an integral part of periodontal therapy. Enamel and cementum show a smooth surface clinically after debridement with the naked eye, but numerous surface irregularities can be detected microscopically. Air polishing is safe and effective when used by trained professionals. Aims: The aim of the study is to evaluate and compare the surface roughness of cementum by using an air polishing device and conventional root planing with hand instruments. Materials and Methods: A total of 45 extracted teeth stored in saline were divided into three groups randomly - Group A (conventional root planing), Group B (hand instrumentation and air polishing), and Group C (air polishing alone) - with 15 samples each. Samples were evaluated for surface roughness by using profilometer. Six parameters were checked for surface roughness. Statistical Analysis Used: The data were collected, charted, and analyzed using one-way ANOVA with post hoc LSD method for pairwise comparisons. Results: Least amount of surface roughness was achieved with Group C when compared with Group A and Group B. These differences were statistical significant (P < 0.0001). Conclusions: Air polishing can effectively smoothen the root surface by removing surface irregularities which are produced hand/ultrasonic instruments. Profilometer can be effectively used to measure the surface roughness.

Some Novel Results Involving Prototypical Computation of Zagreb Polynomials and Indices for SiO4 Embedded in a Chain of Silicates.

A topological index as a graph parameter was obtained mathematically from the graph's topological structure. These indices are useful for measuring the various chemical characteristics of chemical compounds in the chemical graph theory. The number of atoms that surround an atom in the molecular structure of a chemical compound determines its valency. A significant number of valency-based molecular invariants have been proposed, which connect various physicochemical aspects of chemical compounds, such as vapour pressure, stability, elastic energy, and numerous others. Molecules are linked with numerical values in a molecular network, and topological indices are a term for these values. In theoretical chemistry, topological indices are frequently used to simulate the physicochemical characteristics of chemical molecules. Zagreb indices are commonly employed by mathematicians to determine the strain energy, melting point, boiling temperature, distortion, and stability of a chemical compound. The purpose of this study is to look at valency-based molecular invariants for SiO4 embedded in a silicate chain under various conditions. To obtain the outcomes, the approach of atom-bond partitioning according to atom valences was applied by using the application of spectral graph theory, and we obtained different tables of atom-bond partitions of SiO4. We obtained exact values of valency-based molecular invariants, notably the first Zagreb, the second Zagreb, the hyper-Zagreb, the modified Zagreb, the enhanced Zagreb, and the redefined Zagreb (first, second, and third). We also provide a graphical depiction of the results that explains the reliance of topological indices on the specified polynomial structure parameters.

School closures help reduce the spread of COVID-19: A pre- and post-intervention analysis in Pakistan.

Closing schools to control COVID-19 transmission has been globally debated, with concerns about children's education and well-being, and also because of the varied effectiveness of the intervention in studies across the world. This paper aims to determine the effect of school closure policy on the incidence of COVID-19 in Pakistan. A Difference-in-Differences (DiD) analysis compared changes in COVID-19 incidence across cities that completely (Islamabad) and partially (Peshawar) closed schools during the second wave of COVID-19 in Pakistan. Effects of closing (November 2020) and reopening schools (February 2021) were assessed in Islamabad and Peshawar 10 and 20 days after policy implementation. In Islamabad, there was a greater decline in cases than in Peshawar when schools closed. After 10-days, the average reduction of daily COVID-19 incidence in Islamabad was lower by 89 cases (95% CI: -196, 18), due to complete school closure, with a relative reduction of 125 cases (95% CI: -191, -59) compared to Peshawar. Similarly, the relative increase in Islamabad after schools re-opened was 107 cases (95% CI: 46, 167) compared to Peshawar. After 20-days, the average daily COVID-19 incidence in both cities declined after school were closed (Islamabad: -81 [95% CI: -150, -13] versus Peshawar: -80 [95% CI: -148, -12]). COVID-19 incidence appeared to decline after schools reopened as well (Islamabad: -116 [95% CI: -230, -3] versus Peshawar: -30 [95% CI: -124, 63]). However, Peshawar's decline is not statistically significant. These results control for changes in testing as well as a daily time trend. The magnitude and speed of reduction in cases with a complete school closure, and a similar but reverse trend of increasing cases upon reopening, suggests that closing schools reduces COVID-19 transmission in communities. However, there are learning-loss and well-being costs for children and their parents.

Impact of school closures and reopening on COVID-19 caseload in 6 cities of Pakistan: An Interrupted Time Series Analysis.

Schools were closed all over Pakistan on November 26, 2020 to reduce community transmission of COVID-19 and reopened between January 18 and February 1, 2021. However, these closures were associated with significant economic and social costs, prompting a review of effectiveness of school closures to reduce the spread of COVID-19 infections in a developing country like Pakistan. A single-group interrupted time series analysis (ITSA) was used to measure the impact of school closures, as well as reopening schools, on daily new COVID-19 cases in 6 major cities across Pakistan: Lahore, Karachi, Islamabad, Quetta, Peshawar, and Muzaffarabad. However, any benefits were contingent on continued closure of schools, as cases bounced back once schools reopened. School closures are associated with a clear and statistically significant reduction in COVID-19 cases by 0.07 to 0.63 cases per 100,000 population, while reopening schools is associated with a statistically significant increase. Lahore is an exception to the effect of school closures, but it too saw an increase in COVID-19 cases after schools reopened in early 2021. We show that closing schools was a viable policy option, especially before vaccines became available. However, its social and economic costs must also be considered.