Tropical Data: Approach and Methodology as Applied to Trachoma Prevalence Surveys

PURPOSE: Population-based prevalence surveys are essential for decision-making on interventions to achieve trachoma elimination as a public health problem. This paper outlines the methodologies of Tropical Data, which supports work to undertake those surveys. METHODS: Tropical Data is a consortium of partners that supports health ministries worldwide to conduct globally standardised prevalence surveys that conform to World Health Organization recommendations. Founding principles are health ministry ownership, partnership and collaboration, and quality assurance and quality control at every step of the survey process. Support covers survey planning, survey design, training, electronic data collection and fieldwork, and data management, analysis and dissemination. Methods are adapted to meet local context and needs. Customisations, operational research and integration of other diseases into routine trachoma surveys have also been supported. RESULTS: Between 29th February 2016 and 24th April 2023, 3373 trachoma surveys across 50 countries have been supported, resulting in 10,818,502 people being examined for trachoma. CONCLUSION: This health ministry-led, standardised approach, with support from the start to the end of the survey process, has helped all trachoma elimination stakeholders to know where interventions are needed, where interventions can be stopped, and when elimination as a public health problem has been achieved. Flexibility to meet specific country contexts, adaptation to changes in global guidance and adjustments in response to user feedback have facilitated innovation in evidence-based methodologies, and supported health ministries to strive for global disease control targets

Immunological correlates of apparent protection in exposed yet HIV-1 sero-negative Ugandans

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Distinct patterns of peripheral HIV-1-specific interferon- gamma responses in exposed HIV-1-seronegative individuals.

It is unclear how human immunodeficiency virus (HIV) type 1-specific immune responses in exposed seronegative (ESN) individuals differ from those in HIV-1-infected subjects. By use of overlapping peptides spanning Gag, Tat, Nef, Vif, Vpr, and Vpu, peripheral blood mononuclear cells from ESN individuals, their seropositive (SP) partners, and unexposed seronegative control subjects were screened for interferon- gamma production. Responses were more frequent (95.7% vs. 20%), of a higher magnitude (9-fold), and of wider breadth (median number of peptides recognized, 18 vs. 2.5) in SP than in ESN individuals. Peptides recognized by ESN individuals were less frequently recognized by their SP partners. SP subjects infrequently recognized peptides from Vif, and such responses were subdominant; among ESN individuals, this HIV-1 protein was most frequently recognized. Immunodominant peptides recognized by SP subjects tended to be from relatively conserved regions, whereas peptides recognized by ESN individuals were associated with slow disease progression

Recent HIV-1 infection in a high-risk Ugandan cohort: implications for Phase IIB test-of-concept HIV vaccine trials.

Assessment of vaccine efficacy on end points used in Phase IIB test-of-concept trials will require taking into consideration the effect of variables correlated with the end points and distribution of the variables within subgroups of the trial population. Here we report that evaluation of sexual activity in vaccinees and longitudinal collection of plasma viral load data from putative transmitters prior to transmission will contribute to the plausible assessment of efficacy against acquisition of infection. Data also suggest that efficacy on post-infection end points may depend on whether transmission pairs are matched or mismatched for HLA class I alleles

HIV type 1 antigen-responsive CD4+ T-lymphocytes in exposed yet HIV Type 1 seronegative Ugandans.

CD4(+) T cell help is important for the functionality of CD8(+) cytotoxic T-lymphocytes (CTLs) in limiting viral replication and may contribute to mediation of apparent resistance to HIV-1 infection in exposed seronegative (ESN) individuals. Using five HIV-1 antigens in an intracellular cytokine assay, the presence of specific antigen-responsive interferon- gamma-positive (IFN-gamma(+)) CD69(+) CD4(+) T-lymphocytes was evaluated in ESNs, their seropositive partners, and unexposed seronegative controls. Ten ESNs (five females, five uncircumcised males) were identified from 10 HIV-1 serodiscordant couples with a history of frequent unprotected sexual intercourse. All ESNs and controls were negative on two EIAs and for HIV-1 proviral DNA. The frequency of ESNs with antigen-responsive IFN-gamma(+) CD69(+) CD4(+) T-lymphocytes ranged from three to five of eight for the different HIV-1 antigens. Six of eight ESNs tested had a positive response to at least one of the five antigens. Responses were on average 3.5 times higher among seropositives compared to ESNs and absent in the five unexposed controls. A negative correlation was noted between responses in ESNs and the plasma viral load of their seropositive spouse. Clade-specific and cross-clade reactivity were noted in both ESNs and seropositive partners tested. The findings confirm that ESNs are in a state of HIV-1-specific immune activation and suggest that HIV-1-specific IFN-gamma(+) CD69(+) CD4(+) T-lymphocytes in addition to HIV-1-specific CD8(+) CTLs already described by others are potential immunological correlates of protection from persistent HIV-1 infection

Tropical Data: Approach and Methodology as Applied to Trachoma Prevalence Surveys

Population-based prevalence surveys are essential for decision-making on interventions to achieve trachoma elimination as a public health problem. This paper outlines the methodologies of Tropical Data, which supports work to undertake those surveys. Tropical Data is a consortium of partners that supports health ministries worldwide to conduct globally standardised prevalence surveys that conform to World Health Organization recommendations. Founding principles are health ministry ownership, partnership and collaboration, and quality assurance and quality control at every step of the survey process. Support covers survey planning, survey design, training, electronic data collection and fieldwork, and data management, analysis and dissemination. Methods are adapted to meet local context and needs. Customisations, operational research and integration of other diseases into routine trachoma surveys have also been supported. Between 29 February 2016 and 24 April 2023, 3373 trachoma surveys across 50 countries have been supported, resulting in 10,818,502 people being examined for trachoma. This health ministry-led, standardised approach, with support from the start to the end of the survey process, has helped all trachoma elimination stakeholders to know where interventions are needed, where interventions can be stopped, and when elimination as a public health problem has been achieved. Flexibility to meet specific country contexts, adaptation to changes in global guidance and adjustments in response to user feedback have facilitated innovation in evidence-based methodologies, and supported health ministries to strive for global disease control targets

Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study

Background: Human genetic factors are important determinants of malaria risk. We investigated associations between multiple candidate polymorphisms—many related to the structure or function of red blood cells—and risk for severe Plasmodium falciparum malaria and its specific phenotypes, including cerebral malaria, severe malaria anaemia, and respiratory distress. Methods: We did a case-control study in Kilifi County, Kenya. We recruited as cases children presenting with severe malaria to the high-dependency ward of Kilifi County Hospital. We included as controls infants born in the local community between Aug 1, 2006, and Sept 30, 2010, who were part of a genetics study. We tested for associations between a range of candidate malaria-protective genes and risk for severe malaria and its specific phenotypes. We used a permutation approach to account for multiple comparisons between polymorphisms and severe malaria. We judged p values less than 0·005 significant for the primary analysis of the association between candidate genes and severe malaria. Findings: Between June 11, 1995, and June 12, 2008, 2244 children with severe malaria were recruited to the study, and 3949 infants were included as controls. Overall, 263 (12%) of 2244 children with severe malaria died in hospital, including 196 (16%) of 1233 with cerebral malaria. We investigated 121 polymorphisms in 70 candidate severe malaria-associated genes. We found significant associations between risk for severe malaria overall and polymorphisms in 15 genes or locations, of which most were related to red blood cells: ABO, ATP2B4, ARL14, CD40LG, FREM3, INPP4B, G6PD, HBA (both HBA1 and HBA2), HBB, IL10, LPHN2 (also known as ADGRL2), LOC727982, RPS6KL1, CAND1, and GNAS. Combined, these genetic associations accounted for 5·2% of the variance in risk for developing severe malaria among individuals in the general population. We confirmed established associations between severe malaria and sickle-cell trait (odds ratio [OR] 0·15, 95% CI 0·11–0·20; p=2·61 × 10−58), blood group O (0·74, 0·66–0·82; p=6·26 × 10−8), and –α3·7-thalassaemia (0·83, 0·76–0·90; p=2·06 × 10−6). We also found strong associations between overall risk of severe malaria and polymorphisms in both ATP2B4 (OR 0·76, 95% CI 0·63–0·92; p=0·001) and FREM3 (0·64, 0·53–0·79; p=3·18 × 10−14). The association with FREM3 could be accounted for by linkage disequilibrium with a complex structural mutation within the glycophorin gene region (comprising GYPA, GYPB, and GYPE) that encodes for the rare Dantu blood group antigen. Heterozygosity for Dantu was associated with risk for severe malaria (OR 0·57, 95% CI 0·49–0·68; p=3·22 × 10−11), as was homozygosity (0·26, 0·11–0·62; p=0·002). Interpretation: Both ATP2B4 and the Dantu blood group antigen are associated with the structure and function of red blood cells. ATP2B4 codes for plasma membrane calcium-transporting ATPase 4 (the major calcium pump on red blood cells) and the glycophorins are ligands for parasites to invade red blood cells. Future work should aim at uncovering the mechanisms by which these polymorphisms can result in severe malaria protection and investigate the implications of these associations for wider health. Funding: Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative

Tropical Data: Approach and Methodology as Applied to Trachoma Prevalence Surveys

Population-based prevalence surveys are essential for decision-making on interventions to achieve trachoma elimination as a public health problem. This paper outlines the methodologies of Tropical Data, which supports work to undertake those surveys. Tropical Data is a consortium of partners that supports health ministries worldwide to conduct globally standardised prevalence surveys that conform to World Health Organization recommendations. Founding principles are health ministry ownership, partnership and collaboration, and quality assurance and quality control at every step of the survey process. Support covers survey planning, survey design, training, electronic data collection and fieldwork, and data management, analysis and dissemination. Methods are adapted to meet local context and needs. Customisations, operational research and integration of other diseases into routine trachoma surveys have also been supported. Between 29th February 2016 and 24th April 2023, 3373 trachoma surveys across 50 countries have been supported, resulting in 10,818,502 people being examined for trachoma. This health ministry-led, standardised approach, with support from the start to the end of the survey process, has helped all trachoma elimination stakeholders to know where interventions are needed, where interventions can be stopped, and when elimination as a public health problem has been achieved. Flexibility to meet specific country contexts, adaptation to changes in global guidance and adjustments in response to user feedback have facilitated innovation in evidence-based methodologies, and supported health ministries to strive for global disease control targets.</p

Outcomes and Their State-level Variation in Patients Undergoing Surgery With Perioperative SARS-CoV-2 Infection in the USA. A Prospective Multicenter Study

Objective: To report the 30-day outcomes of patients with perioperative SARS-CoV-2 infection undergoing surgery in the USA. Background: Uncertainty regarding the postoperative risks of patients with SARS-CoV-2 exists. Methods: As part of the COVIDSurg multicenter study, all patients aged ≥17 years undergoing surgery between January 1 and June 30, 2020 with perioperative SARS-CoV-2 infection in 70 hospitals across 27 states were included. The primary outcomes were 30-day mortality and pulmonary complications. Multivariable analyses (adjusting for demographics, comorbidities, and procedure characteristics) were performed to identify predictors of mortality. Results: A total of 1581 patients were included; more than half of them were males (n = 822, 52.0%) and older than 50 years (n = 835, 52.8%). Most procedures (n = 1261, 79.8%) were emergent, and laparotomies (n = 538, 34.1%). The mortality and pulmonary complication rates were 11.0 and 39.5%, respectively. Independent predictors of mortality included age ≥70 years (odds ratio 2.46, 95% confidence interval [1.65-3.69]), male sex (2.26 [1.53-3.35]), ASA grades 3-5 (3.08 [1.60-5.95]), emergent surgery (2.44 [1.31-4.54]), malignancy (2.97 [1.58-5.57]), respiratory comorbidities (2.08 [1.30-3.32]), and higher Revised Cardiac Risk Index (1.20 [1.02-1.41]). While statewide elective cancelation orders were not associated with a lower mortality, a sub-analysis showed it to be associated with lower mortality in those who underwent elective surgery (0.14 [0.03-0.61]). Conclusions: Patients with perioperative SARS-CoV-2 infection have a significantly high risk for postoperative complications, especially elderly males. Postponing elective surgery and adopting non-operative management, when reasonable, should be considered in the USA during the pandemic peaks