Over-Prescription and Overuse of Antimicrobials in the Eastern Mediterranean Region: The Urgent Need for Antimicrobial Stewardship Programs with Access, Watch, and Reserve Adoption.

Excessive antimicrobial use contributes to the development of antimicrobial resistance. In the Eastern Mediterranean region (EMR), there is dearth of information on the prevalence of antimicrobial use in patients hospitalized in acute healthcare settings, clinical indications, types of antimicrobials prescribed, and quality indicators for prescriptions. Between September and December 2019, seven countries in the EMR conducted a standardized point prevalence survey. All patients present in the hospital wards at 8 a.m. on the day of the survey constituted the sample population. We collected data, including patient characteristics, antimicrobials received, therapeutic indication according to predefined lists, and markers of prescribing quality. The survey included data from 139 hospitals in seven countries. Among the 19,611 inpatients surveyed, 11,168 patients received at least one antimicrobial {crude prevalence: 56.9% (95%CI: 56.2-57.6%). The top three classes of antimicrobials prescribed were third-generation cephalosporins (26.7%), beta-lactam penicillins (18.1%), and imidazole derivatives (n = 1655, 9.8%). Carbapenems were most frequently prescribed for the treatment of healthcare-associated infections. Compliance with quality indicators of antimicrobial use was limited where treatment guidelines were available for 41% of antimicrobial prescriptions and targeted antimicrobial treatment represented 21% of therapeutic indications. Overall hospital antimicrobial use was high in countries of the EMR, pointing to the need to design and implement context-specific antimicrobial stewardship programs to optimize antimicrobial use and reduce antimicrobial resistance.

Worldwide prevalence of hepatitis B virus and hepatitis C virus among patients with cirrhosis at country, region, and global levels: a systematic review.

BACKGROUND: Empirical, updated country-level estimates on the proportion of cirrhosis attributable to viral hepatitis are required. We estimated the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in patients with cirrhosis at country, regional, and global levels as an approximation for the fractions of cirrhosis attributable to viral hepatitis. METHODS: In this systematic review, we searched MEDLINE, Embase, Web of Science, and Scielo between Jan 1, 1993, and Aug 1, 2021. Studies were eligible if they reported on the prevalence of both HBV and HCV infection in representative studies of at least 20 patients with cirrhosis. Studies were excluded if they used first-generation HCV assays or were from a selected population of patients with cirrhosis (eg, patients selected based on specific causes, veterans, injecting drug users). Two authors (CJA and CdM) selected and extracted aggregated data from the selected publications. Data were extracted for study recruitment period, age, sex, and cause of cirrhosis, among others. Data about heavy alcohol consumption and non-alcoholic fatty liver disease (NAFLD) were also extracted when available. Aggregated data from studies from key publications were requested from the authors of the original study if selection of patients was unclear or information on causes was missing. We estimated the country-specific prevalence of causes of cirrhosis by pooling study-level data from the same country using a random-effects model. Subsequently, we estimated the regional (WHO region and UN subregion) and global prevalence by weighting the country-specific prevalence by the number of new liver cancer cases that occurred in 2020, as estimated in GLOBOCAN. The study was registered with PROSPERO, CRD42020149323. FINDINGS: Our database searches identified 21 338 records, and a further nine records were identified by scanning references of key publications. After excluding duplicates and assessing full-text articles for eligibility, 520 publications from 86 countries or territories (and reporting on 1 376 503 patients with cirrhosis) were included in the systematic review. The prevalence of HBV infection was lower among patients with cirrhosis in Europe, the Americas, and Oceania (UN subregional prevalence ranges 3-14%) than in Africa and Asia (8-61%). HCV infection prevalence was heterogenous, even within regions (12-83%). The combined prevalence of HBV and HCV infection exceeded 50% in most Asian and African regions. Globally, among patients with cirrhosis, 42% had HBV infection and 21% had HCV infection. The contribution of heavy alcohol use was highest in Europe (country range 16-78%), the Americas (17-52%), and Oceania (15-37%) and lowest in Asia (0-41%). Data on NAFLD were limited. INTERPRETATION: HBV and HCV could account for almost two thirds of the global burden of cirrhosis. With the availability of effective interventions for the prevention or treatment of HBV and HCV, the data presented in this study will help to effectively allocate resources towards viral hepatitis elimination and to design interventions at the country level. FUNDING: International Agency for Research on Cancer, World Health Organization.

United for dignity: four strategic shifts to get to zero leprosy by 2030.

Leprosy, or Hansen's disease, is a curable infectious disease caused by the bacillus M. leprae. In 1991, the World Health Assembly WHA44.9 set the goal for "elimination of leprosy as a public health problem" as less than one case on treatment per 10 000 population by 2000. Since then, global leprosy strategies have focused on reducing the prevalence of the disease at country level and reducing transmission. Early detection and prompt treatment with multidrug therapy, the keystone for leprosy control, led to the achievement of this goal at global level by 2000, and in almost all countries, at least at the national level, by 2015.

The global hepatitis delta virus (HDV) epidemic: what gaps to address in order to mount a public health response?

BACKGROUND: Co-infection between hepatitis B virus (HBV) and hepatitis delta virus (HDV) causes the severest chronic hepatitis and is associated with a high risk of cirrhosis and hepatocellular carcinoma (HCC). The Global Health Sector Strategy on Viral Hepatitis called for the elimination of hepatitis (- 65% mortality and - 90% incidence) by 2030. Our aims were to summarize key points of knowledge and to identify the gaps that need to be addressed to mount a public health response to HDV. METHODS: We performed a current literature review in terms of epidemiology by WHO regions, genotypes distribution and their pathogenicity, factors associated with HDV infection, mortality due to HDV infection, testing strategies and treatment. RESULTS: Prevalence of infection and genotypes are heterogeneous distributed, with highest prevalence in foci around the Mediterranean, in the Middle East, and in Central, Northern Asia and Eastern Asia. Persons who inject drugs (PWID) and migrants from highly endemic areas are highly affected. While antibody detection tests are available, HDV RNA tests of current infection are not standardized nor widely available. The few therapeutic options, including lofartinib, are not widely available; however several new and promising agents have entered clinical trials. CONCLUSION: HDV infection is an poorly known cause of chronic liver disease. To mount a public health response, we need a better description of the HDV epidemic, standardized testing strategies and better treatment options.

Injection practices in 2011-2015: a review using data from the demographic and health surveys (DHS).

BACKGROUND: Reuse of injection devices to give healthcare injections decreased from 39.8 to 5.5% between 2000 and 2010, but trends since 2011 have not been described. We reviewed results of Demographic and Health Surveys (DHS) to describe injection practices worldwide from 2011 to 2015. METHODS: We searched the DHS Internet site for data published on injection practices conducted in countries from 2011 to 2015, extracted information on frequency (number of healthcare injections per person in the last 12 months) and safety (proportion of syringes and needles taken from a new, unopened package). We compared gender groups and WHO regions in terms of frequency and safety. For countries with data available, we compared injection practices 2004-2010 and 2011-2015. RESULTS: Since 2011, 40 of 92 countries (43%) that conducted DHS surveys reported on injection practices. On average, the frequency of injection was 1.64 per person per year (from 3.84 in WHO Eastern Mediterranean region to 1.18 in WHO African region). Among those, 96.1% of injections reportedly used new injection devices (from 90.2% in the WHO Eastern Mediterranean region to 98.8% in the WHO Western Pacific region). On average, women received more injections per year (1.85) than men (1.41). Among 16 (40%) countries with data in 2004-2010 and 2011-2015, 69% improved in terms of safety. The annual number of unsafe injections reduced in 81% of countries. In Pakistan, the number of unsafe injections was the highest and did not decrease between 2006 and 2012. CONCLUSIONS: Injection practices have continued to improve in most countries worldwide, although the Eastern Mediterranean region in particular still faces unsafe practices that are not improving. Further efforts are needed to eliminate unsafe injection practices in health care settings, including through the use of reuse-prevention devices. Despite some limitations, DHS is an easily available method to measure progress over time.

How far are we from viral hepatitis elimination service coverage targets?

INTRODUCTION: In 2016, the Global Health Sector Strategy (GHSS) on viral hepatitis called for elimination of viral hepatitis as a major public health threat by 2030 (i.e. 90% reduction in incidence and 65% in mortality). In 2017, WHO's first-ever Global Hepatitis Report presented the baseline values for each of the core indicators of the strategy. We review the challenges and opportunities that lie ahead in order to reach the 2030 service coverage targets. DISCUSSION: Three-dose coverage of hepatitis B vaccine in infancy reached 84% in 2015 (2030 target: 90%); however, only 39% received the timely birth dose (2030 target: 90%). Blood safety (97% of blood units screened with quality assurance, 2030 target: 100%) and injection safety (5% unsafe injections, 2030 target: 0%) had made substantial progress while harm reduction fell short (27 syringe and needle sets distributed per person who injects drugs per year, 2030 target: 300). Worldwide, 9% and 20% of the HBV- and HCV-infected population respectively, were aware of their status (2030 targets: 90%). In the short term, to reach the 2020 target of diagnosing 50% of those infected, 107 million HBV infected persons and 15 million HCV infected persons should be urgently diagnosed. Overall, in 2015, less than 10% of known infected persons were on HBV treatment or had started HCV treatment (2030 targets: 80%). CONCLUSIONS: The prevention component of elimination is on track with respect to hepatitis B vaccination, blood safety, and injection safety. However, coverage of the hepatitis B vaccine timely birth dose requires a substantial increase, particularly in sub-Saharan Africa, and harm reduction needs to be taken to scale as injecting drug use accounts for a third of mortality from HCV infection. A promising but limited start in hepatitis testing and treatment needs to be followed by immediate and sustained action so that we reach the service coverage targets required to achieve elimination by 2030. Treating persons coinfected with HIV and hepatitis viruses is particularly urgent and needs to be promoted in the context of the HIV response.

Visceral leishmaniasis is preventable in a highly endemic village in West Bengal, India.

In 2004, following a cluster of kala-azar cases in Chatrakhali, West Bengal, India, we screened and treated this endemic village for leishmaniasis infection. In 2005, following new reports of kala-azar, we screened the village again and conducted a retrospective cohort study (exposure period: August 2004 to July 2005). We defined an incident case of leishmaniasis as a new seropositive sample (>or=1:1600 dilution in a direct agglutination test) in a person seronegative in 2004. We obtained information about potential risk factors and calculated the relative risk (RR) of infection for exposure to these factors. One hundred and fifty (20%) of the 751 residents acquired leishmaniasis in 1 year. Factors associated with infection included residing in homes with mud walls (RR 4.3), dampness in the home (RR 2.5), proximity to bodies of water (RR 2.5) and livestock ownership (RR 2.4). Sleeping dressed (RR 0.4), or under a bed net (RR 0.5) or in a cot (RR 0.6) were associated with a lower risk. High rates of infection indicated that transmission persisted in this community. Poor housing conditions were associated with a higher risk, while personal protection measures against vectors were effective. Major housing improvement and personal protection efforts are needed to protect this vulnerable population from leishmaniasis.

Increasing incidence of malaria in Kurseong, Darjeeling District, West Bengal, India, 2000-2004.

In Kurseong, Darjeeling District, India, malaria caused concern but insufficient information was available. We analysed surveillance data to estimate the burden of malaria and to examine trends. Confirmed malaria reports were reviewed and climatic records were collected. The annual parasite incidence (API; number of cases/population) and the annual blood examination rate (ABER; number of slides examined/population) were calculated to assess case detection activities, and the slide positivity rate (SPR; number of slides positive/total number examined) was calculated to assess transmission trends. The API increased from 2 to 7.8 per 1000 population between 2000 and 2004 (no deaths), with a high incidence among all age groups. Two foothill areas with forests and slow-moving streams accounted for 88% of the 697 cases in 2004. The average 2000-2004 ABER was 4.8%, below the 10% examination target of the National Anti-Malaria Programme. The proportion of Plasmodium falciparum increased from 62% in 2000 to 77% in 2004. More than 50% of P. falciparum in the area were chloroquine resistant. The SPR increased from 8.1% in 2000 to 11.9% in 2004 and peaked during monsoons. Annual rainfall increased from 2000 to 2003. Malaria transmission increased, with an increasing proportion of P. falciparum in a context of resistance to chloroquine. We recommend increasing case detection and using artemisinin-based combination therapy to treat P. falciparum malaria.

The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide.

BACKGROUND/AIMS: End-stage liver disease accounts for one in forty deaths worldwide. Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are well-recognized risk factors for cirrhosis and liver cancer, but estimates of their contributions to worldwide disease burden have been lacking. METHODS: The prevalence of serologic markers of HBV and HCV infections among patients diagnosed with cirrhosis or hepatocellular carcinoma (HCC) was obtained from representative samples of published reports. Attributable fractions of cirrhosis and HCC due to these infections were estimated for 11 WHO-based regions. RESULTS: Globally, 57% of cirrhosis was attributable to either HBV (30%) or HCV (27%) and 78% of HCC was attributable to HBV (53%) or HCV (25%). Regionally, these infections usually accounted for >50% of HCC and cirrhosis. Applied to 2002 worldwide mortality estimates, these fractions represent 929,000 deaths due to chronic HBV and HCV infections, including 446,000 cirrhosis deaths (HBV: n=235,000; HCV: n=211,000) and 483,000 liver cancer deaths (HBV: n=328,000; HCV: n=155,000). CONCLUSIONS: HBV and HCV infections account for the majority of cirrhosis and primary liver cancer throughout most of the world, highlighting the need for programs to prevent new infections and provide medical management and treatment for those already infected.

Injection use in two districts of Pakistan: implications for disease prevention.

OBJECTIVE: To estimate the annual number of injections per person in Sindh province of Pakistan and to describe their distribution with regard to prescribers, settings, and safety. DESIGN: A population-based cross-sectional study in July-September 2001. SETTING: Lyari, an urban town in Karachi district; and Digri, a rural subdistrict in Mirpur Khas district. STUDY PARTICIPANTS: We selected a population-based cluster sample of 1150 individuals aged > or =3 months. We interviewed one person per household for the number of encounters they had with health care providers, number and types of injections received, safety circumstances, and cost of injections during the past 3 months. Main outcome measure. The number of injections per person per year. RESULTS: After adjusting for age and sex, 68% of participants had received at least one injection in the previous 3 months (13.6 injections/person/year). The majority of the respondents received injections at the clinics of qualified general practitioners (n = 571, 67%) by dispensers (644, 76%). Most of the injections (n = 3446, 96%) were for curative purposes. A freshly opened syringe was used for only 454 (53%) of the injections. The average fee for receiving an injection was Rs. 51 (US$ 0.8). CONCLUSION: Injections are overused in Pakistan's Sindh province and the ratios of injection per capita that we found are among the highest ever reported. INTERVENTIONS: are needed to substantially reduce injection prescription among private health care providers who prescribe most of the injections received by the population.

Could the WHO model list of essential medicines do more for the safe and appropriate use of injections?

A national drug policy addressing the safe and appropriate use of injections is an important element to prevent overuse and unsafe use of injections. Because the World Health Organization World Health Organization Model List of Essential Medicines is a keystone of national drug policies, the authors examined the way it addresses injection practices. They reviewed the 11th World Health Organization Model List of Essential Medicines to collect information on (1) injectable medicines, (2) diluents, and (3) the recommendations regarding the procurement of injection devices. Of 306 active ingredients on the list, 135 (44%) are mentioned in injectable form. Of these, 41 (30%) need diluents for reconstitution. The list does not mention the need to procure appropriate diluents, injection devices, and safety boxes in quantities that match the quantities of injectable medicines. In addition, the list provides limited information that can be used to forecast the needs of injection devices to administer the injectable medicines that are included in the list. Future revisions of the World Health Organization Model List of Essential Medicines should attempt to reduce the number of injectable formulations on the basis of evidence. In addition, the list should specify that when injectable medicines are being supplied, diluents, single-use syringes, and safety boxes should be supplied. The volume of syringes needed for administration should be specified for each injectable medication on the list to facilitate the forecasting of the needs of injection devices.

Factors associated with fulminant liver failure during an outbreak among injection drug users with acute hepatitis B.

Death related to acute hepatitis B occurs in approximately 1% of patients. We investigated an outbreak of hepatitis B virus (HBV) infections among injection drug users (IDUs) resulting in several deaths. We conducted a case-control study of fulminant (case patients) and nonfulminant (control patients) HBV infections. We directly sequenced the entire HBV genome from fulminant and nonfulminant cases. From October 1998 to July 2000, 21 acute HBV infections, including 10 fulminant hepatitis B cases, were identified. The median age was 30 (range, 18-49) years, 12 (57%) were female, 20 (95%) were American Indians, and 20 (95%) reported injecting illicit drugs. All patients with fulminant hepatitis B died (case-fatality rate = 47.6%). Case patients (n = 5) and control patients (n = 9) were similar with respect to age, sex, race, and hepatitis C virus serostatus. All case patients used acetaminophen during their illness compared with 44% of control patients (P =.08). Compared with control patients, case patients lost more weight in the 6 months before illness (P =.04); during their illness, they used more alcohol (P =.03) and methamphetamine (P =.04). All 9 isolates sequenced were genotype D, shared 99.7% homology, and included mutations previously described in association with fulminant hepatitis B. In conclusion, a high prevalence of exposure to factors potentiating hepatic damage with acute hepatitis B contributed to the outbreak's high mortality rate; mutations present in the outbreak strain might also have been a factor. Improved vaccination coverage among IDUs has the potential to prevent similar outbreaks in the future.

Trypanosoma brucei gambiense trypanosomiasis in Terego county, northern Uganda, 1996: a lot quality assurance sampling survey.

We estimated the pre-intervention prevalence of Trypanosoma brucei gambiense (Tbg) trypanosomiasis using the lot quality assurance sampling (LQAS) methods in 14 parishes of Terego County in northern Uganda. A total of 826 participants were included in the survey sample in 1996. The prevalence of laboratory confirmed Tbg trypanosomiasis adjusted for parish population sizes was 2.2% (95% confidence interval =1.1-3.2). This estimate was consistent with the 1.1% period prevalence calculated on the basis of cases identified through passive and active screening in 1996-1999. Ranking of parishes in four categories according to LQAS analysis of the 1996 survey predicted the prevalences observed during the first round of active screening in the population in 1997-1998 (P < 0.0001, by chi-square test). Overall prevalence and ranking of parishes obtained with LQAS were validated by the results of the population screening, suggesting that these survey methods may be useful in the pre-intervention phase of sleeping sickness control programs.

The global burden of disease attributable to contaminated injections given in health care settings.

As part of the 2000 Global Burden of Disease study, we quantified the death and disability from injection-associated infections with hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). We modelled the fraction of incident infections attributable to health care injections in the year 2000 on the basis of the annual number of injections, the proportion of injections administered with reused equipment, the probability of transmission following percutaneous exposure, the prevalence of active infection, the prevalence of immunity and the total incidence. Infections in 2000 were converted into disability-adjusted life years (DALYs) in 2000-2030 using natural history parameters, background mortality, duration of disease, disability weights, age weights and a 3% discount rate. Four Global Burden of Disease regions where reuse of injection equipment in the absence of sterilization was negligible were excluded from the analysis. In the remaining 10 regions, in 2000, persons received an average of 3.4 injections per year, 39.3% of which were given with reused equipment. In 2000, contaminated injections caused an estimated 21 million HBV infections, two million HCV infections and 260,000 HIV infections, accounting for 32%, 40% and 5%, respectively, of new infections for a burden of 9,177,679 DALYs between 2000 and 2030. Injection overuse and unsafe practices account for a substantial burden of death and disability worldwide. There is a need for policies and plans for the safe and appropriate use of injections in countries where practices are poor.