Social Media-Based Interventions for Health Behavior Change in Low- and Middle-Income Countries: Systematic Review.

BACKGROUND: Despite the wealth of evidence regarding effective health behavior change techniques using digital interventions to focus on residents of high-income countries, there is limited information of a similar nature for low- and middle-income countries. OBJECTIVE: The aim of this review is to identify and describe the available literature on effective social media-based behavior change interventions within low- and middle-income countries. METHODS: This systematic review was conducted in accordance with the 2009 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched PubMed, Embase, Elsevier, CINAHL, PsycInfo, and Global Index Medicus, and the final search was conducted on April 6, 2021. We excluded studies published before 2000 because of the subject matter. We included studies that evaluated interventions conducted at least partly on a social media platform. RESULTS: We identified 1832 studies, of which 108 (5.89%) passed title-abstract review and were evaluated by full-text review. In all, 30.6% (33/108) were included in the final analysis. Although 22 studies concluded that the social media intervention was effective, only 13 quantified the level of social media engagement, of which, few used theory (n=8) or a conceptual model (n=5) of behavior change. CONCLUSIONS: We identified gaps in the settings of interventions, types and sectors of interventions, length of follow-up, evaluation techniques, use of theoretical and conceptual models, and discussions of the privacy implications of social media use. TRIAL REGISTRATION: PROSPERO CRD42020223572; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=223572.

Sensitivity and specificity of herpes simplex virus-2 serological assays among HIV-infected and uninfected urban Ugandans.

Herpes simplex virus type 2 (HSV-2) is a risk factor for HIV-1 infection. We characterized HSV-2 serology assay performance in HIV-positive and HIV-negative Africans. Serostatus for HSV-2 and HIV-1 was determined in 493 serum specimens stored from a community HSV-2 prevalence survey in Kampala, Uganda. HSV-2 serology by Focus HerpeSelect ELISA, Biokit HSV-2 rapid assay and Kalon HSV-2 was compared with HSV-2 Western blot (WB) according to HIV-1 serostatus. Sensitivity/specificity was: 99.5%/70.2% for Focus, 97.0%/86.4% for Biokit and 97.5%/96.2% for Kalon. Focus with Biokit confirmation improved sensitivity/specificity (99.4%/96.8%, respectively). Use of a higher Focus index value cut-off of 2.2 instead of 1.1 increased specificity from 70.2% to 92.4%. Kalon had higher specificity than Focus (P < 0.001). Of commercially available HSV-2 serological assays, Kalon alone, or Focus ELISA followed by Biokit confirmation perform best. Improved HSV-2 assays are needed for HSV-2 and HIV-1 public health activities in Africa.

Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.

BACKGROUND: Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. METHODS: We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, > or = 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. RESULTS: A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed. CONCLUSIONS: Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)

An excess of rare genetic variation in ABCE1 among Yorubans and African-American individuals with HIV-1.

Signatures of natural selection occur throughout the human genome and can be detected at the sequence level. We have re-sequenced ABCE1, a host candidate gene essential for HIV-1 capsid assembly, in European- (n=23) and African-descent (Yoruban; n=24) reference populations for genetic variation discovery. We identified an excess of rare genetic variation in Yoruban samples, and the resulting Tajima's D was low (-2.27). The trend of excess rare variation persisted in flanking candidate genes ANAPC10 and OTUD4, suggesting that this pattern of positive selection can be detected across the 184.5 kb examined on chromosome 4. Owing to ABCE1's role in HIV-1 replication, we re-sequenced the candidate gene in three small cohorts of HIV-1-infected or resistant individuals. We were able to confirm the excess of rare genetic variation among HIV-1-positive African-American individuals (n=53; Tajima's D=-2.34). These results highlight the potential importance of ABCE1's role in infectious diseases such as HIV-1.

Severe illness and death among injecting drug users in Scotland: a case-control study.

Between April and September 2000, 60 injecting drug users in Scotland died or were hospitalized with severe illness. Laboratory investigations suggested that Clostridium novyi and other bacteria were important aetiological agents. To determine associated environmental/behavioural factors a case-control study was undertaken with 19 'definite' and 32 'probable' cases in Glasgow, Scotland. For every deceased case (n=19), up to three proxy individuals were interviewed. Three controls were identified for each case. Multivariate logistic regression analyses compared (i) all cases and controls; (ii) definite cases and matched controls; (iii) probable cases and matched controls. In all three analyses injecting into muscle or skin and injecting most of the time with a filter used by someone else were the variables most strongly associated with illness. Comparing only muscle-injecting cases and controls, cases were significantly more likely to have injected larger amounts of heroin per average injection than were controls. The findings make an important epidemiological contribution to the understanding of the public health and clinical implications of the contamination of illicit drugs by histotoxic clostridia.

HLA-DQ6 and ingestion of contaminated water: possible gene-environment interaction in an outbreak of Leptospirosis.

Leptospirosis is a zoonosis that can cause severe multisystem disease. While host gene-environment interactions likely modify infectious disease susceptibility, including for leptopsirosis, this has not been documented. In a 1998 leptospirosis outbreak investigation among triathletes in a lake swim, swallowing lake-water was a disease risk-factor. We used genomic DNA from 85 anonymized blood-sample remainders from that investigation to examine the association of laboratory-confirmed leptospirosis with gene polymorphisms (TNF-alpha alleles and serologically defined genotypes for HLA-DRB1 and HLA-DQB1). HLA-DQ6-positive triathletes had increased risk of laboratory-confirmed leptospirosis (OR=2.8, P=0.04) compared to DQ6-negatives. DQ6-positive triathletes swallowing lake-water had greatest risk (OR 8.46, P< or =0.001). This first report of a genetic risk-factor affecting susceptibility to leptospirosis is also the first documented gene-environment interaction (DQ6 and swallowed water) affecting infectious disease susceptibility. Based on these preliminary findings, we hypothesize a role for superantigens in leptospirosis and underscore the importance of outbreak investigations for understanding infectious disease gene-environment interactions.

Haemophilus influenzae Type b disease among Amish children in Pennsylvania: reasons for persistent disease.

OBJECTIVE: To identify reservoirs of Haemophilus influenzae type b (Hib) pharyngeal carriage and assess barriers to vaccination among 2 Amish communities in Pennsylvania. METHODS: We investigated recent cases, performed community surveys for Hib vaccination coverage and pharyngeal carriage, and administered a questionnaire assessing vaccination knowledge and attitudes to 298 members of 2 Amish communities (A and B) in Pennsylvania and, as a comparison group, 136 non-Amish family members who participated in state immunization clinics. From December 1999 to February 2000, 8 cases of invasive Hib disease occurred among children who were 5 years of age or younger in Pennsylvania. Six of the case-patients were from Amish communities. None of the children had been vaccinated. RESULTS: Among children who were 5 years of age or younger, Hib vaccine coverage was low in the 2 Amish communities: A (9 [28%] of 32) and B (3 [7%] of 41) compared with the non-Amish group (19 [95%] of 20). Hib carriage prevalence was higher in both Amish communities than in the non-Amish group (A: 3%; B: 8%; non-Amish: 0%). More households in community B had 1 or more Hib carriers than in community A (8 [28%] of 29 vs 3 [9%] of 32). Among Amish parents who did not vaccinate their children, only 25% (13 of 51) identified either religious or philosophical objections as a factor; 51% (26 of 51) reported that vaccinating was not a priority compared with other activities of daily life. Seventy-three percent (36 of 49) would vaccinate their children if vaccination were offered locally. CONCLUSIONS: Undervaccinated communities in the United States still exist and allow circulation of Hib strains, resulting in disease among susceptible children. Identification of undervaccinated populations, such as the Amish, and targeted education and vaccination campaigns are essential to achieving elimination of Hib disease.

Surveillance for meningococcal disease and strategies for use of conjugate meningococcal vaccines in the United States.

BACKGROUND: Neisseria meningitidis is a leading cause of bacterial meningitis in US; new capsular type-specific conjugate vaccines offer an opportunity for improved control of meningococcal disease. We evaluated the relative burdens of invasive meningococcal disease in US and examined the projected impact of various meningococcal conjugate vaccination strategies on rates of meningococcal disease. METHODS: Meningococcal disease incidence rates were determined from active, population-based surveillance in selected US areas. Models were created to determine impact of vaccination of infants, toddlers, adolescents or college students with meningococcal conjugate vaccines, with assumptions for vaccine coverage, efficacy and duration of protection. Although we examined possible conjugate vaccine formulations including serogroups A, C, Y and W-135, the final vaccine impact analysis excluded serogroups A and W-135. Outcome measures were cumulative meningococcal disease incidence, and incidence 10 years after initiating vaccination among 0-22-year-olds. RESULTS: In models of serogroup C+Y meningococcal conjugate vaccination of infants, toddlers and adolescents, the cumulative incidence of meningococcal disease was reduced by 54, 48 and 25%, respectively; the toddler strategy had the greatest impact per dose. After 10 years of routine meningococcal conjugate vaccination, meningococcal disease could be reduced by 50% and deaths by 64%. CONCLUSIONS: Use of meningococcal conjugate vaccine could markedly reduce meningococcal disease incidence. Our data, along with vaccine formulation and vaccination program considerations, will be important in determining the optimal choice of vaccination strategy.

Effect of mutations in Gag on assembly of immature human immunodeficiency virus type 1 capsids in a cell-free system.

Studies of HIV-1 capsid formation in a cell-free system revealed that capsid assembly occurs via an ordered series of assembly intermediates and requires host machinery. Here we use this system to examine 12 mutations in HIV-1 Gag that others studied previously in intact cells. With respect to capsid formation, these mutations generally produced the same phenotype in the cell-free system as in cells, indicating the cell-free system's high degree of fidelity. Analysis of assembly intermediates reveals that a mutation in the distal region of CA (322 LDeltaS) and truncations proximal to the second cys-his box in NC block multimerization of Gag at early stages in the cell-free capsid assembly pathway. In contrast, mutations in the region of amino acids 56-68 (located in the proximal portion of MA) inhibit assembly at a later point in the pathway. Other mutations, including truncations distal to the first cys-his box in NC and mutations in the distal half of MA (88HDeltaG, 85YDeltaG, Delta104-115, and Delta115-129), do not affect formation of immature capsids in the cell-free system. These data provide new information on the role of different domains in Gag during the early events of capsid assembly.

Developmental pathways of dendritic cells in vivo: distinct function, phenotype, and localization of dendritic cell subsets in FLT3 ligand-treated mice.

We have recently shown that Flt3 ligand administration dramatically increases dendritic cell (DC) numbers in various mouse tissues. This has enabled the identification of distinct mature DC subpopulations. These have been designated: population C (CD11c(bright) CD11b(bright)), D (CD11c(bright) CD11b(dull)), and E (CD11c(bright) CD11b(negative)) This report demonstrates that the mature DC subsets (C, D, and E) from Flt3 ligand-treated mice differ with respect to phenotype, geographic localization, and function. The myeloid Ags CD11b, F4/80, and Ly-6C are predominantly expressed by population C, but not D or E. In addition, a subset of population C-type DC expresses 33D1 and CD4. In contrast, DC within population D and E selectively express the lymphoid-related DC markers CD8alpha, DEC 205, CD1d, as well as CD23, elevated levels of CD117 (c-kit), CD24 (HSA), CD13, and CD54. Immunohistology indicates that the different DC subsets reside in distinct microenvironments, with populations D and E residing in the T cell areas of the white pulp, while DC within population C localize in the marginal zones. These DC subpopulations showed different capacities to phagocytose FITC-zymosan and to secrete IL-12 upon stimulation with Staphylococcus aureus cowan I strain + IFN-gamma + granulocyte-macrophage-CSF. Population C-type DC were more phagocytic but secreted little inducible IL-12 while population D- and E-type DC showed poor phagocytic capacity and secreted considerably higher levels of IL-12. These results underscore the importance of viewing DC development in vivo, as an interplay between distinct lineages and a maturational dependence on specific microenvironmental signals.

A multistep, ATP-dependent pathway for assembly of human immunodeficiency virus capsids in a cell-free system.

To understand the mechanism by which human immunodeficiency virus type 1 (HIV) capsids are formed, we have reconstituted the assembly of immature HIV capsids de novo in a cell-free system. Capsid authenticity is established by multiple biochemical and morphologic criteria. Known features of the assembly process are closely reproduced, indicating the fidelity of the cell-free reaction. Assembly is separated into co- and posttranslational phases, and three independent posttranslational requirements are demonstrated: (a) ATP, (b) a detergent-sensitive host factor, and (c) a detergent-insensitive host subcellular fraction that can be depleted and reconstituted. Assembly appears to proceed by way of multiple intermediates whose conversion to completed capsids can be blocked by either ATP depletion or treatment with nondenaturing detergent. Specific subsets of these intermediates accumulate upon expression of various assembly-defective Gag mutants in the cell-free system, suggesting that each mutant is blocked at a particular step in assembly. Furthermore, the accumulation of complexes of similar sizes in cells expressing the corresponding mutants suggests that comparable intermediates may exist in vivo. From these data, we propose a multi-step pathway for the biogenesis of HIV capsids, in which the assembly process can be disrupted at a number of discrete points.

Vitamin A therapy for children with respiratory syncytial virus infection: a multicenter trial in the United States.

BACKGROUND: High dose vitamin A therapy is effective in reducing morbidity and mortality associated with measles infection. Children with acute respiratory syncytial virus (RSV) infection have low serum vitamin A concentrations. METHODS: We performed a multicenter, randomized, placebo-controlled trial of high dose vitamin A therapy among 239 children 1 month to 6 years of age to determine whether high dose vitamin A therapy would reduce morbidity associated with RSV infection. RESULTS: There were no differences between the vitamin A and placebo recipients for most clinical outcomes; however, vitamin A recipients had-longer hospital stays than placebo recipients (5.0 days vs. 4.4 days, P = 0.01) after enrollment. This effect was significant for children who were older than 1 year (who also had received the highest doses of vitamin A), particularly among those at low risk for complications of RSV infection and those enrolled during the second study season. Serum retinol levels at enrollment were inversely correlated with severity of illness. CONCLUSIONS: We found no evidence of a beneficial effect of vitamin A for the treatment of RSV infection in children in the United States. There may be groups of children for which vitamin A has an adverse effect, resulting in longer hospital stays.

A eukaryotic cytosolic chaperonin is associated with a high molecular weight intermediate in the assembly of hepatitis B virus capsid, a multimeric particle.

We have established a system for assembly of hepatitis B virus capsid, a homomultimer of the viral core polypeptide, using cell-free transcription-linked translation. The mature particles that are produced are indistinguishable from authentic viral capsids by four criteria: velocity sedimentation, buoyant density, protease resistance, and electron microscopic appearance. Production of unassembled core polypeptides can be uncoupled from production of capsid particles by decreasing core mRNA concentration. Addition of excess unlabeled core polypeptides allows the chase of the unassembled polypeptides into mature capsids. Using this cell-free system, we demonstrate that assembly of capsids proceeds by way of a novel high molecular weight intermediate. Upon isolation, the high molecular weight intermediate is productive of mature capsids when energy substrates are manipulated. A 60-kD protein related to the chaperonin t-complex polypeptide 1 (TCP-1) is found in association with core polypeptides in two different assembly intermediates, but is not associated with either the initial unassembled polypeptides or with the final mature capsid product. These findings implicate TCP-1 or a related chaperonin in viral assembly and raise the possibility that eukaryotic cytosolic chaperonins may play a distinctive role in multimer assembly apart from their involvement in assisting monomer folding.

Temporal regulation in development: negative and positive cis regulators dictate the precise timing of expression of a Drosophila chorion gene.

We have used germ-line transformation to dissect the cis regulatory elements responsible for the transcriptional control of an internally marked Drosophila chorion gene (s15-P) during development. A 73-base-pair segment of the proximal 5'-flanking DNA contains sequences essential for the tissue-specific expression and the precise "late" temporal regulation of that gene. A substitute s36-1 segment of similar location can provide the tissue-specific function and imparts an early temporal regulation characteristic of gene s36-1. Within the regulatory DNA of s15-P, at least three adjacent elements are recognizable: an essential operationally positive element (TCACGT) that is shared by s36-1 and other chorion genes, irrespective of temporal specificity; a second positive element that is required for the normal late expression of s15-P; and, farthest upstream, a negative element that represses precocious expression during the early choriogenic stages.

Pineal transplants in oculo: limitations on the ability of collateral sprouts of foreign neurons to establish normal function.

The pineal gland is innervated by sympathetic neurons whose cell bodies are located in the superior cervical ganglia. This pathway, which carries information concerning environmental lighting to the gland, is important for maintaining a circadian rhythm in the activity of the pineal enzyme serotonin N-acetyltransferase (NAT). Lesioning this pathway blocks the normal nighttime increase in NAT activity. Following transplantation of the pineal gland to the anterior chamber of the eye, the gland becomes reinnervated by collateral sprouts of sympathetic neurons that innervate the iris. In addition, a day-night rhythm in NAT activity is restored to the transplanted glands (Moore, 1975; Bäckström et al., 1976). These findings raise the possibility that the neural regulation of pineal function may be restored to normal by collateral sprouts of foreign neurons. To determine whether this is the case, other aspects of the neural regulation of NAT activity were examined in transplanted and in situ pineal glands. When the dark period was extended into the normal light period, NAT activity decreased to daytime values in both groups, suggesting that, in both cases, darkness is only effective in maintaining high levels of NAT activity at certain times during the day-night cycle. In contrast to their similar responses to extended darkness, the 2 groups of pineal glands responded differently to a brief pulse of light during the dark period. While the light exposure caused a dramatic decrease in nighttime NAT activity in in situ pineal glands, it produced no change in this enzyme activity in transplanted glands.(ABSTRACT TRUNCATED AT 250 WORDS)

A histochemical study of the adrenergic innervation of the rat pineal gland: evidence for overlap of the innervation from the two superior cervical ganglia and for sprouting following unilateral denervation.

The rat pineal gland receives sympathetic innervation, via the right and left internal carotid nerves, from neurons whose cell bodies are located in the two superior cervical ganglia. Using fluorescence microscopy, we have examined the density and distribution of fluorescent profiles in the pineal gland after lesioning of the internal carotid nerves. Thirty-two hours after sectioning both internal carotid nerves, the density of the fluorescent profiles was 3% of that seen in sham-operated controls, indicating that the lesioned fibers had degenerated. Thirty-two hours after sectioning one internal carotid nerve, the density of the processes was decreased to approximately 50% of the control value. The magnitude of the decrease following a unilateral lesion was similar on both the right and left halves of the gland. Thus, the results suggest that each internal carotid nerve innervates both sides of the pineal gland. The implications of this overlap in the innervation from the two internal carotid nerves for recovery of pineal function after a unilateral lesion are discussed. Sections of pineal glands were also analyzed at later time points after a unilateral lesion. Two weeks after cutting one internal carotid nerve, the density of the fluorescent profiles had increased to greater than 80% of the control value. When the contralateral internal carotid nerve was cut 2 weeks after a unilateral lesion and the pineal gland was examined 32 h later, the density of the fluorescent profiles had decreased to 2% of the sham value. This suggests that all of the compensatory increase in adrenergic processes that takes place following the unilateral lesion is due to sprouting of the contralateral internal carotid nerve rather than to regeneration of the lesioned internal carotid nerve or to sprouting and ingrowth of other adrenergic neurons. It remains to be determined what, if any, functional significance this sprouting has, since the neurally dependent circadian rhythm in serotonin N-acetyltransferase activity in the pineal gland is restored to normal within 32 h after a unilateral lesion; that is, before significant sprouting has occurred.