AmBisome Monotherapy and Combination AmBisome-Miltefosine Therapy for the Treatment of Visceral Leishmaniasis in Patients Coinfected With Human Immunodeficiency Virus in India: A Randomized Open-Label, Parallel-Arm, Phase 3 Trial.

BACKGROUND: Visceral leishmaniasis (VL) in patients with human immunodeficiency virus (HIV) presents an increasingly important patient cohort in areas where both infections are endemic. Evidence for treatment is sparce, with no high-quality studies from the Indian subcontinent. METHODS: This is a randomized, open-label, parallel-arm, phase 3 trial conducted within a single hospital in Patna, India. One hundred and fifty patients aged ≥18 years with serologically confirmed HIV and parasitologically confirmed VL were randomly allocated to 1 of 2 treatment arms, either a total 40 mg/kg intravenous liposomal amphotericin B (AmBisome; Gilead Pharmaceuticals) administered in 8 equal doses over 24 days or a total 30 mg/kg intravenous AmBisome administered in 6 equal doses given concomitantly with a total 1.4 g oral miltefosine administered through 2 daily doses of 50 mg over 14 days. The primary outcome was intention-to-treat relapse-free survival at day 210, defined as absence of signs and symptoms of VL or, if symptomatic, negative parasitological investigations. RESULTS: Among 243 patients assessed for eligibility, 150 were recruited between 2 January 2017 and 5 April 2018, with no loss to follow-up. Relapse-free survival at day 210 was 85% (64/75; 95% CI, 77-100%) in the monotherapy arm, and 96%, (72/75; 90-100%) in the combination arm. Nineteen percent (28/150) were infected with concurrent tuberculosis, divided equally between arms. Excluding those with concurrent tuberculosis, relapse-free survival at day 210 was 90% (55/61; 82-100%) in the monotherapy and 97% (59/61; 91-100%) in the combination therapy arm. Serious adverse events were uncommon and similar in each arm. CONCLUSIONS: Combination therapy appears to be safe, well tolerated, and effective, and halves treatment duration of current recommendations. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry India (CTRI/2015/05/005807; the protocol is available online at https://osf.io/avz7r).

Omission of quality assurance during data entry in public health research from India: Is there an elephant in the room?

As the adage, "Garbage in, Garbage out" goes, data entry errors may lead to erroneous results and conclusions. Quality assurance during data entry is one of the most neglected components of research and is conspicuously missing in most of the reporting standards. In this study, we reviewed research studies published in Indian Journal of Public Health and Indian Journal of Community Medicine during 2014-2016 and determined the proportion of papers reporting on quality assurance during data entry. Of 110 papers, only 6 (5.5%) papers explicitly included a statement about data quality assurance, with two studies reported to have performed double entry and validation, considered the gold standard in quality-assurance of data entry. This is highly unacceptable. We hereby appeal to the community of researchers, peer reviewers, and journal editors in India to pay attention to this important aspect of research and make reporting of quality assurance of data entry mandatory in every published paper.

Plain Packaging in Tobacco Control: A Bibliometric Analysis.

The tobacco epidemic is affecting 8 million people with 1.2 million deaths worldwide. The Framework Convention on Tobacco Control (FCTC) was adopted by the World Health Organization (WHO) Member States in 2003 to counter the growing tobacco menace. Articles 11 and 13 of WHO FCTC suggest plain packaging of tobacco products to reduce the visibility and make tobacco products look less attractive. The current bibliometric analysis was conducted to analyze the visibility and impact of the scientific productions contributing to plain packaging globally. The bibliometric analysis allowed a quantitative analysis of all scientific publications indexed in Scopus. The sample was defined using the keywords "plain packaging OR standardized packaging" AND "tobacco." Five broad bibliometric domains were assessed for analysis: namely, scientific production, authors, sources or journals, countries, and thematic areas using R programming v4.2.2 and VOSviewer. The total number of documents published regarding plain packaging in tobacco control from 1992 till mid-2022 was determined. Australia tops the list with 99 publications, followed by the United Kingdom, United States, New Zealand, Canada, France, India, Netherlands, Spain, and Egypt. The author citation network showcases the link between the 21 top documents, with a minimum of 50 citations per document. The two main indicators assessed were the total number of articles published in the journal and the h index. Bibliometric indicators in this study illustrated that scientific publications/efforts to implement the WHO FCTC guideline concerning plain packing laws were neglected in most countries.

Prevalence and determinants of asymptomatic Leishmania infection in HIV-infected individuals living within visceral leishmaniasis endemic areas of Bihar, India.

People living with HIV (PLHIV) have an increased risk of developing visceral leishmaniasis (VL) and poor outcomes compared to HIV negative individuals. Here, we aim to establish the prevalence and determinants of asymptomatic Leishmania infection (ALI) in a cohort of PLHIV in Bihar, India. We hoped to evaluate optimal diagnostic algorithms to detect ALI in PLHIV. We conducted a cross-sectional survey of PLHIV ≥18 years of age with no history or current diagnosis of VL or post kala-azar dermal leishmaniasis (PKDL) at anti-retroviral therapy centres within VL endemic districts of Bihar. ALI was defined as a positive rK39 enzyme-linked immunosorbent assay (ELISA), rK39 rapid diagnostic test (RDT) and/or quantitative polymerase chain reaction (qPCR). Additionally, the urinary Leishmania antigen ELISA was evaluated. Determinants for ALI were established using logistic regression and agreement between diagnostic tests calculated using Cohen's Kappa. A total of 1,296 PLHIV enrolled in HIV care, 694 (53.6%) of whom were female and a median age of 39 years (interquartile range 33-46), were included in the analysis. Baseline prevalence of ALI was 7.4% (n = 96). All 96 individuals were positive by rK39 ELISA, while 0.5% (n = 6) and 0.4% (n = 5) were positive by qPCR and rK39 RDT, respectively. Negligible or weak agreement was seen between assays. Independent risk factors for ALI were CD4 counts <100 (OR 3.1; 95% CI 1.2-7.6) and CD4 counts 100-199 (OR = 2.1;95% CI:1.1-4.0) compared to CD4 counts ≥300, and a household size ≥5 (OR = 1.9;95% CI:1.1-3.1). A total of 2.2% (n = 28) participants were positive by Leishmania antigen ELISA, detecting 20 additional participants to the asymptomatic cohort. Prevalence of ALI in PLHIV in VL endemic villages in Bihar was relatively high. Using the Leishmania antigen ELISA, prevalence increased to 9.0%. Patients with low CD4 counts and larger household size were found to have significantly higher risk of ALI. Trial Registration: Clinical Trial Registration CTRI/2017/03/008120.

Prevalence and predictors of exclusive breastfeeding in urban slums, Bihar.

OBJECTIVE: Various socio-cultural factors influence infant feeding practices and thus early childhood nutrition and child survival in India. This study aimed to examine the prevalence of exclusive breastfeeding, its promoters and barriers in urban slums of Bihar, India. METHODS: We conducted a community based cross-sectional survey involving 297 mothers living in slum settlements in Bihar. Data were collected using structured questionnaire on exclusive breastfeeding practices, and the factors that could influence this. Descriptive analysis was done to estimate the prevalence of exclusive breastfeeding and regression model was performed to identify the predictors of exclusive breastfeeding. RESULTS: Only 23% of mothers initiate breastfeeding within 1 hour of delivery and 27.6% mothers practise exclusive breastfeeding up to six months. Mother's education was found to be associated with duration of exclusive breastfeeding (OR 11, 95% CI 2-59). Term babies were more likely to be breastfed exclusively for six months than pre-term babies (OR 8.6, 95% CI 1.6-47.6). Antenatal care visits and completing immunization were significantly associated with duration of exclusive breastfeeding (P < 0.001). The majority of mothers acquire exclusive breastfeeding knowledge through television/radio (OR 68, 95% CI 5.5-832.5) and newspaper advertisements (OR 14, 95% CI 2.6-76). CONCLUSION: Prevalence of exclusive breastfeeding up to six months of age and early initiation of breastfeeding remains low in slums of Bihar. Exclusive breastfeeding and early initiation of breastfeeding rates could be improved by educating and counselling mothers during health facility contacts by primary care providers.

Quality of life perceptions amongst patients co-infected with Visceral Leishmaniasis and HIV: A qualitative study from Bihar, India.

BACKGROUND: Co-infection with Visceral Leishmaniasis (commonly known as Kala Azar, KA) and Human Immunodeficiency Virus (HIV) is increasingly being diagnosed among patients in Bihar. This qualitative study is the first assessment of self-reported quality of life among patients co-infected with KA-HIV in the Asian context. METHODS: We conducted semi-structured, in-depth interviews and adopted an inductive thematic analysis to generate evidence on the quality of life of patients co-infected with KA and HIV. Patients were purposively sampled until saturation was attained. RESULTS: We found that patients highly valued income or livelihood potential and health as indicators of a good quality life, and routinely went into debt accessing care in the private setup. This was due to perceptions of poor quality of care in the government setup and a lack of knowledge regarding available government services at the district level. KA symptoms were often misdiagnosed in the private sector as seasonal fever, while care providers found it difficult to disentangle the clinical symptoms of KA and HIV; hence, patients presented late to district hospitals. Patients perceived a high level of stigma, largely due to their HIV status, and routinely reported that HIV had "destroyed" their life. CONCLUSIONS: Inadequate social support and referral pathways that were not conducive to patient needs negatively impacted patients' quality of life. The dual burden of poverty interacting with the severity and chronicity of KA-HIV co-infection means financial support, increased community engagement, and collaborative decision making are crucial for co-infected patients. Increased provider awareness of co-infection and effective stigma-reduction interventions should be integrated to ensure that appropriate and effective access to care is possible for this vulnerable population. A sustainable long-term strategy requires a people-centered approach wherein the perceptions and life circumstances of patients are taken into account in the medical decision making process.

Refused and referred-persistent stigma and discrimination against people living with HIV/AIDS in Bihar: a qualitative study from India.

OBJECTIVES: This study aimed to explore barriers to accessing care, if any, among people living with HIV/AIDS (PLHA) in two districts of Bihar. We also aimed to assess attitudes towards PLHA among healthcare providers and community members. DESIGN: This qualitative study used an exploratory study design through thematic analysis of semistructured, in-depth interviews. SETTING: Two districts were purposively selected for the study, namely the capital Patna and a peripheral district located approximately 100 km from Patna, in order to glean insights from a diverse sample of respondents. PARTICIPANTS: Our team purposively selected 71 participants, including 35 PLHA, 10 community members and 26 healthcare providers. RESULTS: The overarching theme that evolved from these data through thematic coding identified that enacted stigma and discrimination interfere with each step in the HIV care continuum for PLHA in Bihar, India, especially outside urban areas. The five themes that contributed to these results include: perception of HIV as a dirty illness at the community level; non-consensual disclosure of HIV status; reliance on identifying PLHA to guide procedures and resistance to universal precautions; refusal to treat identified PLHA and referrals to other health centres for treatment; and inadequate knowledge and fear among health providers with respect to HIV transmission. CONCLUSIONS: The continued presence of discriminatory and stigmatising attitudes towards PLHA negatively impacts both disclosure of HIV status as well as access to care and treatment. We recognise a pressing need to improve the knowledge of HIV transmission, and implement universal precautions across all health facilities in the state, not just to reduce stigma and discrimination but also to ensure proper infection control. In order to improve treatment adherence and encourage optimal utilisation of services, it is imperative that the health system invest more in stigma reduction in Bihar and move beyond more ineffective, punitive approaches.