Spatial heterogeneity in projected leprosy trends in India

Background: Leprosy is caused by infection with Mycobacterium leprae and is characterized by peripheral nerve damage and skin lesions. The disease is classified into paucibacillary (PB) and multibacillary (MB) leprosy. The 2012 London Declaration formulated the following targets for leprosy control: (1) global interruption of transmission or elimination by 2020, and (2) reduction of grade-2 disabilities in newly detected cases to below 1 per million population at a global level by 2020. Leprosy is treatable, but diagnosis, access to treatment and treatment adherence (all necessary to curtail transmission) represent major challenges. Globally, new case detection rates for leprosy have remained fairly stable in the past decade, with India responsible for more than half of cases reported annually. Methods: We analyzed publicly available data from the Indian Ministry of Health and Family Welfare, and fit linear mixed-effects regression models to leprosy case detection trends reported at the district level. We assessed correlation of the new district-level case detection rate for leprosy with several state-level regressors: TB incidence, BCG coverage, fraction of cases exhibiting grade 2 disability at diagnosis, fraction of cases in children, and fraction multibacillary. Results: Our analyses suggest an endemic disease in very slow decline, with substantial spatial heterogeneity at both district and state levels. Enhanced active case finding was associated with a higher case detection rate. Conclusions: Trend analysis of reported new detection rates from India does not support a thesis of rapid progress in leprosy control

COVID-19 among adults living with HIV:correlates of mortality among public sector healthcare users in Western Cape, South Africa

Abstract Introduction While a large proportion of people with HIV (PWH) have experienced SARS‐CoV‐2 infections, there is uncertainty about the role of HIV disease severity on COVID‐19 outcomes, especially in lower‐income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH. Methods We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS‐CoV‐2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID‐19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period. Results Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first‐diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults. Conclusions Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID‐19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized

Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa

Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1)

Accessing HIV care may lead to earlier ascertainment of comorbidities in health care clients in Khayelitsha, Cape Town.

Successful antiretroviral rollout in South Africa has greatly increased the health of the HIV-positive population, and morbidity and mortality in PLHIV can increasingly be attributed to comorbidities rather than HIV/AIDS directly. Understanding this disease burden can inform health care planning for a growing population of ageing PLHIV. Anonymized routine administrative health data were analysed for all adults who accessed public health care in 2016-2017 in Khayelitsha subdistrict (Cape Town, South Africa). Selected comorbidities and age of ascertainment for comorbidities were described for all HIV-positive and HIV-negative healthcare clients, as well as for a subset of women who accessed maternal care. There were 172 937 adult individuals with a median age of 37 (IQR:30-48) years in the virtual cohort, of whom 48% (83 162) were HIV-positive. Median age of ascertainment for each comorbidity was lower in HIV-positive compared to HIV-negative healthcare clients, except in the case of tuberculosis. A subset of women who previously accessed maternal care, however, showed much smaller differences in the median age of comorbidity ascertainment between the group of HIV-positive and HIV-negative health care clients, except in the case of chronic kidney disease (CKD). Both HIV-positive individuals and women who link to maternal care undergo routine point-of-care screening for common diseases at younger ages, and this analysis suggests that this may lead to earlier diagnosis of common comorbidities in these groups. Exceptions include CKD, in which age of ascertainment appears lower in PLHIV than HIV-negative groups in all analyses suggesting that age of disease onset may indeed be earlier; and tuberculosis for which age of incidence has previously been shown to vary according to HIV status

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI)

Background: During a stimulated cycle of in vitro fertilisation or intracytoplasmic sperm injection (IVF/ICSI), women receive daily doses of gonadotropin follicle-stimulating hormone (FSH) to induce multifollicular development in the ovaries. A normal response to stimulation (e.g. retrieval of 5 to 15 oocytes) is considered desirable. Generally, the number of eggs retrieved is associated with the dose of FSH. Both hyper-response and poor response are associated with an increased chance of cycle cancellation. In hyper-response, this is due to increased risk of ovarian hyperstimulation syndrome (OHSS), while poor response cycles are cancelled because the quantity and quality of oocytes is expected to be low. Clinicians often individualise the FSH dose using patient characteristics predictive of ovarian response. Traditionally, this meant women's age, but increasingly, clinicians use various ovarian reserve tests (ORTs). These include basal FSH (bFSH), antral follicle count (AFC), and anti-Müllerian hormone (AMH). It is unclear whether individualising FSH dose improves clinical outcomes. This review updates the 2018 version. Objectives: To assess the effects of individualised gonadotropin dose selection using markers of ovarian reserve in women undergoing IVF/ICSI. Search methods: We searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, CENTRAL, MEDLINE, Embase, and two trial registers in February 2023. Selection criteria: We included randomised controlled trials (RCTs) that compared (a) different doses of FSH in women with a defined ORT profile (i.e. predicted low, normal, or high responders based on AMH, AFC, and/or bFSH) or (b) an individualised dosing strategy (based on at least one ORT measure) versus uniform dosing or a different individualised dosing algorithm. Data collection and analysis: We used standard Cochrane methodological procedures. Primary outcomes were live birth/ongoing pregnancy and severe OHSS. Main results: We included 26 studies, involving 8520 women (6 new studies added to 20 studies included in the previous version). We treated RCTs with multiple comparisons as separate trials for the purpose of this review. Meta-analysis was limited due to clinical heterogeneity. Evidence certainty ranged from very low to low, with the main limitations being imprecision and risk of bias associated with lack of blinding. Direct dose comparisons according to predicted response in women. Due to differences in dose comparisons, caution is required when interpreting the RCTs in predicted low responders. All evidence was low or very low certainty. Effect estimates were very imprecise, and increased FSH dosing may or may not have an impact on rates of live birth/ongoing pregnancy, OHSS, and clinical pregnancy. Similarly, in predicted normal responders (10 studies, 4 comparisons), higher doses may or may not impact the probability of live birth/ongoing pregnancy (e.g. 200 versus 100 international units (IU): odds ratio (OR) 0.88, 95% confidence interval (CI) 0.57 to 1.36; I2 = 0%; 2 studies, 522 women) or clinical pregnancy. Results were imprecise, and a small benefit or harm remains possible. There were too few events for the OHSS outcome to enable inferences. In predicted high responders, lower doses may or may not affect live birth/ongoing pregnancy (OR 0.98, 95% CI 0.66 to 1.46; 1 study, 521 women), severe OHSS, and clinical pregnancy. It is also unclear whether lower doses reduce moderate or severe OHSS (Peto OR 2.31, 95% CI 0.80 to 6.67; 1 study, 521 participants). ORT-algorithm studies. Eight trials compared an ORT-based algorithm to a non-ORT control group. It is unclear whether live birth/ongoing pregnancy and clinical pregnancy are increased using an ORT-based algorithm (live birth/ongoing pregnancy: OR 1.12, 95% CI 0.98 to 1.29; I2 = 30%; 7 studies, 4400 women; clinical pregnancy: OR 1.04, 95% CI 0.91 to 1.18; I2 = 18%; 7 studies, 4400 women; low-certainty evidence). However, ORT algorithms may reduce moderate or severe OHSS (Peto OR 0.60, 95% CI 0.42 to 0.84; I2 = 0%; 7 studies, 4400 women; low-certainty evidence). There was insufficient evidence to determine whether the groups differed in rates of severe OHSS (Peto OR 0.74, 95% CI 0.42 to 1.28; I2 = 0%; 5 studies, 2724 women; low-certainty evidence). Our findings suggest that if the chance of live birth with a standard starting dose is 25%, the chance with ORT-based dosing would be between 25% and 31%. If the chance of moderate or severe OHSS with a standard starting dose is 5%, the chance with ORT-based dosing would be between 2% and 5%. These results should be treated cautiously due to heterogeneity in the algorithms: some algorithms appear to be more effective than others. Authors' conclusions: We did not find that tailoring the FSH dose in any particular ORT population (low, normal, high ORT) affected live birth/ongoing pregnancy rates, but we could not rule out differences, due to sample size limitations. Low-certainty evidence suggests that it is unclear if ORT-based individualisation leads to an increase in live birth/ongoing pregnancy rates compared to a policy of giving all women 150 IU. The confidence interval is consistent with an increase of up to around six percentage points with ORT-based dosing (e.g. from 25% to 31%) or a very small decrease (&lt; 1%). A difference of this magnitude could be important to many women. It is unclear if this is driven by improved outcomes in a particular subgroup. Further, ORT algorithms reduced the incidence of OHSS compared to standard dosing of 150 IU. However, the size of the effect is also unclear. The included studies were heterogeneous in design, which limited the interpretation of pooled estimates. It is likely that different ORT algorithms differ in their effectiveness. Current evidence does not provide a clear justification for adjusting the dose of 150 IU in poor or normal responders, especially as increased dose is associated with greater total FSH dose and cost. It is unclear whether a decreased dose in predicted high responders reduces OHSS, although this would appear to be the most likely explanation for the results.</p

Spatial heterogeneity in projected leprosy trends in India

CITATION: Brook, C. E. et al. 2015. Spatial heterogeneity in projected leprosy trends in India. Parasites & Vectors, 8:542, doi:10.1186/s13071-015-1124-7.The original publication is available at http://parasitesandvectors.biomedcentral.comBackground: Leprosy is caused by infection with Mycobacterium leprae and is characterized by peripheral nerve damage and skin lesions. The disease is classified into paucibacillary (PB) and multibacillary (MB) leprosy. The 2012 London Declaration formulated the following targets for leprosy control: (1) global interruption of transmission or elimination by 2020, and (2) reduction of grade-2 disabilities in newly detected cases to below 1 per million population at a global level by 2020. Leprosy is treatable, but diagnosis, access to treatment and treatment adherence (all necessary to curtail transmission) represent major challenges. Globally, new case detection rates for leprosy have remained fairly stable in the past decade, with India responsible for more than half of cases reported annually. Methods: We analyzed publicly available data from the Indian Ministry of Health and Family Welfare, and fit linear mixed-effects regression models to leprosy case detection trends reported at the district level. We assessed correlation of the new district-level case detection rate for leprosy with several state-level regressors: TB incidence, BCG coverage, fraction of cases exhibiting grade 2 disability at diagnosis, fraction of cases in children, and fraction multibacillary. Results: Our analyses suggest an endemic disease in very slow decline, with substantial spatial heterogeneity at both district and state levels. Enhanced active case finding was associated with a higher case detection rate. Conclusions: Trend analysis of reported new detection rates from India does not support a thesis of rapid progress in leprosy control.http://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-015-1124-7Publisher's versio

Spatial heterogeneity in projected leprosy trends in India.

BackgroundLeprosy is caused by infection with Mycobacterium leprae and is characterized by peripheral nerve damage and skin lesions. The disease is classified into paucibacillary (PB) and multibacillary (MB) leprosy. The 2012 London Declaration formulated the following targets for leprosy control: (1) global interruption of transmission or elimination by 2020, and (2) reduction of grade-2 disabilities in newly detected cases to below 1 per million population at a global level by 2020. Leprosy is treatable, but diagnosis, access to treatment and treatment adherence (all necessary to curtail transmission) represent major challenges. Globally, new case detection rates for leprosy have remained fairly stable in the past decade, with India responsible for more than half of cases reported annually.MethodsWe analyzed publicly available data from the Indian Ministry of Health and Family Welfare, and fit linear mixed-effects regression models to leprosy case detection trends reported at the district level. We assessed correlation of the new district-level case detection rate for leprosy with several state-level regressors: TB incidence, BCG coverage, fraction of cases exhibiting grade 2 disability at diagnosis, fraction of cases in children, and fraction multibacillary.ResultsOur analyses suggest an endemic disease in very slow decline, with substantial spatial heterogeneity at both district and state levels. Enhanced active case finding was associated with a higher case detection rate.ConclusionsTrend analysis of reported new detection rates from India does not support a thesis of rapid progress in leprosy control