Do Oral Cholera Vaccine and Water, Sanitation, and Hygiene Combine to Provide Greater Protection Against Cholera? Results From a Cluster-Randomized Trial of Oral Cholera Vaccine in Kolkata, India.

Background: Oral cholera vaccine (OCV) and incremental improvements in household water, sanitation, and hygiene (WASH) within cholera-endemic areas can reduce cholera risk. However, we lack empiric evaluation of their combined impact. Methods: We evaluated a cluster-randomized, placebo-controlled trial of OCV (Shanchol) in Kolkata, India. The study population included 108 777 individuals, and 106 879 nonpregnant individuals >1 year of age were eligible to receive 2 doses of OCV or placebo. We measured cholera risk in all household members assigned to OCV vs placebo and in all members of households with "Better" vs "Not Better" WASH, where WASH was classified according to validated criteria. Protection was measured by Cox proportional hazard models. Results: Residence in an OCV household was associated with protective effectiveness (PE) of 54% (95% CI, 42%-64%; P < .001) and was similar regardless of Better (PE, 57%; 95% CI, 26%-75%; P = .002) or Not Better (PE, 53%; 95% CI, 40%-64%; P < .001) household WASH. Better WASH household residence was associated with PE of 30% (95% CI, 5%-48%; P = .023) and was similar in OCV (PE, 24%; 95% CI, -26% to 54%; P = .293) and placebo (PE, 29%; 95% CI, -3% to 51%; P = .069) households. When assessed conjointly, residence in OCV households with Better WASH was associated with the greatest PE against cholera at 69% (95% CI, 49%-81%; P < .001). Conclusions: These findings suggest that the combination of a vaccine policy and improved WASH reduces cholera risk more than either would alone, although the magnitude of either intervention was not affected by the other. Future randomized trials investigating OCV and WASH interventions separately and together are recommended to further understand the interaction between OCV and WASH.

Vaccination to Reduce Antimicrobial Resistance Burden-Data Gaps and Future Research.

Antimicrobial resistance (AMR) poses an immediate danger to global health. If unaddressed, the current upsurge in AMR threatens to reverse the achievements in reducing the infectious disease-associated mortality and morbidity associated with antimicrobial treatment. Consequently, there is an urgent need for strategies to prevent or slow the progress of AMR. Vaccines potentially contribute both directly and indirectly to combating AMR. Modeling studies have indicated significant gains from vaccination in reducing AMR burdens for specific pathogens, reducing mortality/morbidity, and economic loss. However, quantifying the real impact of vaccines in these reductions is challenging because many of the study designs used to evaluate the contribution of vaccination programs are affected by significant background confounding, and potential selection and information bias. Here, we discuss challenges in assessing vaccine impact to reduce AMR burdens and suggest potential approaches for vaccine impact evaluation nested in vaccine trials.

Efficacy and safety of praziquantel treatment against Schistosoma mansoni infection among pre-school age children in southern Ethiopia.

BACKGROUND: Preventive chemotherapy with a single dose of praziquantel given to an all-at-risk population through mass drug administration is the cornerstone intervention to control and eliminate schistosomiasis as a public health problem. This intervention mainly targets school age children, and pre-school age children (pre-SAC) are excluded from receiving preventive chemotherapy, partly due to scarcity of data on praziquantel treatment outcomes. METHODS: We conducted active efficacy and safety surveillance of praziquantel treatment among 240 Schistosoma mansoni-infected pre-SAC who received a single dose of praziquantel (40 mg/kg) in southern Ethiopia. The study outcomes were egg reduction rates (ERR) and cure rates (CRs) four weeks after treatment using the Kato-Katz technique and treatment-associated adverse events (AEs) that occurred within 8 days post-treatment. RESULTS: The overall ERR was 93.3% (WHO reference threshold ≥ 90%), while the CR was 85.2% (95% CI = 80.0-89.5%). Baseline S. mansoni infection intensity was significantly associated with CRs, 100% among light infected than moderate (83.4%) or heavy (29.4%) infected children. An increase of 100 in baseline S. mansoni egg count per gram of stool resulted in a 26% (95% CI: 17%, 34%) reduction in the odds of cure. The incidence of experiencing at least one type of AE was 23.1% (95% CI: 18.0%, 29.0%). Stomachache, diarrhea, and nausea were the most common AEs. AEs were mild-to-moderate grade and transient. Pre-treatment moderate (ARR = 3.2, 95% CI: 1.69, 6.14) or heavy infection intensity (ARR = 6.5, 95% CI: 3.62, 11.52) was a significant predictor of AEs (p < 0.001). Sex, age, or soil-transmitted helminth coinfections were not significant predictors of CR or AEs. CONCLUSIONS: Single-dose praziquantel is tolerable and effective against S. mansoni infection among pre-SAC, and associated AEs are mostly mild-to-moderate and transient. However, the reduced CR in heavily infected and AEs in one-fourth of S. mansoni-infected pre-SAC underscores the need for safety and efficacy monitoring, especially in moderate-to-high infection settings. Integrating pre-SACs in the national deworming programs is recommended to accelerate the elimination of schistosomiasis as a public health problem.

Better Existing Water, Sanitation, and Hygiene Can Reduce the Risk of Cholera in an Endemic Setting: Results From a Prospective Cohort Study From Kolkata, India.

Background: Global cholera control efforts rely heavily on effective water, sanitation, and hygiene (WASH) interventions in cholera-endemic settings. Methods: Using data from a large, randomized controlled trial of oral cholera vaccine conducted in Kolkata, India, we evaluated whether natural variations in WASH in an urban slum setting were predictive of cholera risk. From the control population (n = 55 086), baseline WASH data from a randomly selected "training subpopulation" (n = 27 634) were analyzed with recursive partitioning to develop a dichotomous ("better" vs "not better") composite household WASH variable from several WASH features collected at baseline, and this composite variable was then evaluated in a mutually exclusive "validation population" (n = 27 452). We then evaluated whether residents of better WASH households in the entire population (n = 55 086) experienced lower cholera risk using Cox regression models. Better WASH was defined by a combination of 4 dichotomized WASH characteristics including safe source of water for daily use, safe source of drinking water, private or shared flush toilet use, and always handwashing with soap after defecation. Results: Residence in better WASH households was associated with a 30% reduction in risk of cholera over a 5-year period (adjusted hazard ratio, 0.70 [95% confidence interval, .49-.99]; P = .048). We also found that the impact of better WASH households on reducing cholera risk was greatest in young children (0-4 years) and this effect progressively declined with age. Conclusions: The evidence suggests that modest improvements in WASH facilities and behaviors significantly modify cholera risk and may be an important component of cholera prevention and elimination strategies in endemic settings. Clinical Trials Registration. NCT00289224.

Association Among Household Water, Sanitation, and Hygiene (WASH) Status and Typhoid Risk in Urban Slums: Prospective Cohort Study in Bangladesh.

BACKGROUND: Typhoid fever, or enteric fever, is a highly fatal infectious disease that affects over 9 million people worldwide each year, resulting in more than 110,000 deaths. Reduction in the burden of typhoid in low-income countries is crucial for public health and requires the implementation of feasible water, sanitation, and hygiene (WASH) interventions, especially in densely populated urban slums. OBJECTIVE: In this study, conducted in Mirpur, Bangladesh, we aimed to assess the association between household WASH status and typhoid risk in a training subpopulation of a large prospective cohort (n=98,087), and to evaluate the performance of a machine learning algorithm in creating a composite WASH variable. Further, we investigated the protection associated with living in households with improved WASH facilities and in clusters with increasing prevalence of such facilities during a 2-year follow-up period. METHODS: We used a machine learning algorithm to create a dichotomous composite variable ("Better" and "Not Better") based on 3 WASH variables: private toilet facility, safe drinking water source, and presence of water filter. The algorithm was trained using data from the training subpopulation and then validated in a distinct subpopulation (n=65,286) to assess its sensitivity and specificity. Cox regression models were used to evaluate the protective effect of living in "Better" WASH households and in clusters with increasing levels of "Better" WASH prevalence. RESULTS: We found that residence in households with improved WASH facilities was associated with a 38% reduction in typhoid risk (adjusted hazard ratio=0.62, 95% CI 0.49-0.78; P<.001). This reduction was particularly pronounced in individuals younger than 10 years at the first census participation, with an adjusted hazard ratio of 0.49 (95% CI 0.36-0.66; P<.001). Furthermore, we observed an inverse relationship between the prevalence of "Better" WASH facilities in clusters and the incidence of typhoid, although this association was not statistically significant in the multivariable model. Specifically, the adjusted hazard of typhoid decreased by 0.996 (95% CI 0.986-1.006) for each percent increase in the prevalence of "Better" WASH in the cluster (P=.39). CONCLUSIONS: Our findings demonstrate that existing variations in household WASH are associated with differences in the risk of typhoid in densely populated urban slums. This suggests that attainable improvements in WASH facilities can contribute to enhanced typhoid control, especially in settings where major infrastructural improvements are challenging. These findings underscore the importance of implementing and promoting comprehensive WASH interventions in low-income countries as a means to reduce the burden of typhoid and improve public health outcomes in vulnerable populations.

Time to establish an international vaccine candidate pool for potential highly infectious respiratory disease: a community's view.

In counteracting highly infectious and disruptive respiratory diseases such as COVID-19, vaccination remains the primary and safest way to prevent disease, reduce the severity of illness, and save lives. Unfortunately, vaccination is often not the first intervention deployed for a new pandemic, as it takes time to develop and test vaccines, and confirmation of safety requires a period of observation after vaccination to detect potential late-onset vaccine-associated adverse events. In the meantime, nonpharmacologic public health interventions such as mask-wearing and social distancing can provide some degree of protection. As climate change, with its environmental impacts on pathogen evolution and international mobility continue to rise, highly infectious respiratory diseases will likely emerge more frequently and their impact is expected to be substantial. How quickly a safe and efficacious vaccine can be deployed against rising infectious respiratory diseases may be the most important challenge that humanity will face in the near future. While some organizations are engaged in addressing the World Health Organization's "blueprint for priority diseases", the lack of worldwide preparedness, and the uncertainty around universal vaccine availability, remain major concerns. We therefore propose the establishment of an international candidate vaccine pool repository for potential respiratory diseases, supported by multiple stakeholders and countries that contribute facilities, technologies, and other medical and financial resources. The types and categories of candidate vaccines can be determined based on information from previous pandemics and epidemics. Each participant country or region can focus on developing one or a few vaccine types or categories, together covering most if not all possible potential infectious diseases. The safety of these vaccines can be tested using animal models. Information for effective candidates that can be potentially applied to humans will then be shared across all participants. When a new pandemic arises, these pre-selected and tested vaccines can be quickly tested in RCTs for human populations.

Comparing the effectiveness of bivalent and monovalent COVID-19 vaccines against COVID-19 infection during the winter season of 2022-2023: A real-world retrospective observational matched cohort study in the Republic of Korea.

OBJECTIVES: To compare the effectiveness of bivalent and monovalent COVID-19 vaccines throughout the 2022-2023 winter season based on real-world data. METHODS: This retrospective observational matched cohort study used the national vaccination program and a surveillance dataset from the Republic of Korea, and included adults aged >18 years who received bivalent or monovalent COVID-19 vaccines between October 11, 2022, and December 17, 2022. Cox proportional hazard models were used to estimate the hazard ratio for COVID-19 infection between the groups. RESULTS: We included 29,245 matched individuals in the bivalent and monovalent vaccine groups, respectively. The bivalent vaccine recipients showed 12.2% (95% confidence interval [CI] 6.5-17.7%) additional protection against COVID-19 infection compared with the monovalent vaccine recipients. The additional protection provided by bivalent vaccines was significantly higher among residents of long-term care facilities (39.4%, 95% CI 21.6-53.1%). Maximum additional protection was observed 3 to 4 months after completing the vaccination (17.6%, 95% CI 6.6-27.3%). CONCLUSION: Bivalent COVID-19 vaccines showed significantly better protection against infection than monovalent vaccines among adults during the 2022-2023 winter season. Our results highlight that immunization programs with bivalent vaccines comprising recent variants can be an effective measure to prepare for seasonal COVID-19 circulation.

Associations of water, sanitation, and hygiene with typhoid fever in case-control studies: a systematic review and meta-analysis.

BACKGROUND: Water, sanitation, and hygiene (WASH) play a pivotal role in controlling typhoid fever, as it is primarily transmitted through oral-fecal pathways. Given our constrained resources, staying current with the most recent research is crucial. This ensures we remain informed about practical insights regarding effective typhoid fever control strategies across various WASH components. We conducted a systematic review and meta-analysis of case-control studies to estimate the associations of water, sanitation, and hygiene exposures with typhoid fever. METHODS: We updated the previous review conducted by Brockett et al. We included new findings published between June 2018 and October 2022 in Web of Science, Embase, and PubMed. We used the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool for risk of bias (ROB) assessment. We classified WASH exposures according to the classification provided by the WHO/UNICEF Joint Monitoring Programme for Water Supply, Sanitation, and Hygiene (JMP) update in 2015. We conducted the meta-analyses by only including studies that did not have a critical ROB in both Bayesian and frequentist random-effects models. RESULTS: We identified 8 new studies and analyzed 27 studies in total. Our analyses showed that while the general insights on the protective (or harmful) impact of improved (or unimproved) WASH remain the same, the pooled estimates of OR differed. Pooled estimates of limited hygiene (OR = 2.26, 95% CrI: 1.38 to 3.64), untreated water (OR = 1.96, 95% CrI: 1.28 to 3.27) and surface water (OR = 2.14, 95% CrI: 1.03 to 4.06) showed 3% increase, 18% decrease, and 16% increase, respectively, from the existing estimates. On the other hand, improved WASH reduced the odds of typhoid fever with pooled estimates for improved water source (OR = 0.54, 95% CrI: 0.31 to 1.08), basic hygiene (OR = 0.6, 95% CrI: 0.38 to 0.97) and treated water (OR = 0.54, 95% CrI: 0.36 to 0.8) showing 26% decrease, 15% increase, and 8% decrease, respectively, from the existing estimates. CONCLUSIONS: The updated pooled estimates of ORs for the association of WASH with typhoid fever showed clear changes from the existing estimates. Our study affirms that relatively low-cost WASH strategies such as basic hygiene or water treatment can be an effective tool to provide protection against typhoid fever in addition to other resource-intensive ways to improve WASH. TRIAL REGISTRATION: PROSPERO 2021 CRD42021271881.

Prevalence and Determinants of Schistosoma mansoni Infection among Pre-School Age Children in Southern Ethiopia.

School-based deworming program is implemented to control and eliminate Schistosoma mansoni infection in many endemic countries, including Ethiopia. However, pre-school-age children (pre-SAC) are not targeted to receive preventive chemotherapy against S. mansoni infection, partly due to a lack of information on the disease burden. We assessed the prevalence and correlates of S. mansoni infection among pre-SAC in Southern Ethiopia. A total of 1683 pre-SAC aged 4 to 7 years were screened for S. mansoni infection. A multilevel binary logistic regression was fitted to detect the significant determinants of S. mansoni infection. Adjusted odds ratios (AORs) with a 95% confidence interval (CI) were used to identify determinants of S. mansoni infection. The overall prevalence of S. mansoni infection was 14.3% (95% CI: 12.6, 16.0%). S. mansoni infection was significantly higher among 6-year-old (AOR = 2.58, 95% CI: 1.55, 4.27) and 7-year-old children (AOR = 4.63, 95% CI: 2.82, 7.62). Accompanying others to water sources sometimes (AOR = 2.60, 95% CI: 1.12, 6.01) and all the time (AOR = 5.91, 95% CI: 2.51, 13.90), and residing in less than one kilometer from the infested water source (AOR = 3.17, 95% CI: 1.47, 6.83) increased the odds of S. mansoni infection. In conclusion, the prevalence of S. mansoni infection among pre-SAC in the study area was moderate. The study highlights the urgent need to include pre-SAC aged 4 to 7 years in annual preventive chemotherapy campaigns to reduce the risk of possible sources of infection and enhance the achievement of the elimination target.

Development and evaluation of a kangaroo mother care implementation model in South Ethiopia.

AIM: To develop a model for increasing the coverage of kangaroo mother care (KMC), which involved ≥8 h of skin-to-skin contact per day and exclusive breastfeeding, for small babies with birth weight < 2000 g in South Ethiopia. METHODS: A mixed methods study was conducted between June 2017 and January 2019 at four hospitals and their catchment areas. Iterative cycles of implementation, program learning and evaluation were used to optimise KMC implementation models. The study explored the community-facility continuum of care and assessed the proportion of neonates with a birth weight less than 2000 g receiving effective KMC. RESULTS: Three KMC implementation models were tested with Model 2 being the final version. This model included enhanced identification of home births, improved referral linkages, immediate skin-to-skin care initiation in facilities and early contact after discharge. These improvements resulted in 86% coverage of effective facility-based KMC initiation for eligible babies. The coverage was 81.5% at discharge and 57.5% 7 days after discharge. The mean age of babies at KMC initiation was 8.2 days (SD = 5.7). CONCLUSION: The study found that the KMC implementation model was feasible and can lead to substantial population-level KMC coverage for small babies.

Detection of dengue virus infection in children presenting with fever in Hawassa, southern Ethiopia.

Dengue fever is a mosquito-borne viral infection, with rising incidence globally. Eastern Ethiopia has had dengue fever outbreaks in recent years. However, the extent to which the infection contributes to hospital presentation among children with fever in southern Ethiopia is unknown. We examined 407 stored plasma samples collected to investigate the aetiology of fever in children aged at least 2 months and under 13 years presenting to the outpatient of the largest tertiary hospital in southern Ethiopia. We analyzed samples for dengue virus non-structural 1 antigen using enzyme-linked immunosorbent assay. The median (interquartile range) age of the 407 children examined was 20 (10-48) months, and 166 (40.8%) of the children were females. Of 407 samples analyzed, 9 (2.2%) were positive for dengue virus non-structural 1 antigen, of whom 2 were initially treated with antimalarial drugs despite having negative malaria microscopy, and 1 of the 8 patients had a persistent fever at the seventh day of follow-up time. The presence of active dengue virus infection in the study area highlights the need for studies at the community level as well as the integration of dengue diagnostics into fever-management strategies. Further research to characterize circulating strains is warranted.

The interplay between WASH practices and vaccination with oral cholera vaccines in protecting against cholera in urban Bangladesh: Reanalysis of a cluster-randomized trial.

The current global initiative to end Cholera by 2030 emphasizes the use of oral cholera vaccine (OCV) combined with feasible household Water-Sanitation-Hygiene (WASH) interventions. However, little is known about how improved WASH practices and behaviors and OCV interact to reduce the risk of cholera. We reanalyzed two arms of a cluster-randomized trial in urban Bangladesh, to evaluate the effectiveness of OCV given as a 2-dose regimen. One arm (30 clusters, n = 94,675) was randomized to vaccination of persons aged one year and older with OCV, and the other arm (30 clusters, n = 80,056) to no intervention. We evaluated the prevention of cholera by household WASH, classified at baseline using a previously validated rule, and OCV over 2 years of follow-up. When analyzed by assignment to OCV clusters rather than receipt of OCV, in comparison to persons living in "Not Better WASH" households in the control clusters, reduction of severe cholera (the primary outcome) was similar for persons in "Not Better WASH" households in vaccine clusters (46%, 95% CI:24,62), for persons in "Better WASH" households in the control clusters (48%, 95% CI:25,64), and for persons in "Better WASH" households in the vaccine clusters (48%, 95% CI:16,67). In contrast, when analyzed by actual receipt of a complete OCV regimen, , in comparison to persons in "Not Better WASH" households in the control clusters, protection against severe cholera increased steadily from 39% (95% CI:13,58) in residents of "Better WASH" households in the control clusters to 57% (95% CI:35,72) in vaccinated persons in "Not Better WASH" households to 63% (95% CI:21,83) in vaccinated persons in "Better WASH" households. This analysis suggests that improved household WASH and OCV received may interact to provide greater protection against cholera. However, the divergence between findings related to intent to vaccinate versus those pertaining to actual receipt of OCV underscores the need for further research on this topic.

Genetic and non-genetic factors influencing efavirenz population pharmacokinetics among human immunodeficiency virus-1-infected children in Ethiopia.

Despite the potential for efavirenz (EFV) to be an effective alternative antiretroviral agent, its sources of wide inter- and intra-individual pharmacokinetic (PK) variability are not well-characterized in children. We investigated the effects of genetic and non-genetic factors, including demographic, treatment duration, baseline clinical, and biochemical characteristics, on the PKs of EFV through population-PK modeling. Antiretroviral therapy (ART) naïve HIV infected children, 3-16 years (n = 100), were enrolled in Ethiopia and received EFV-based combination ART. EFV concentrations after the first dose and at steady-state collected over a span of 1 year were modeled using population-based methods. A one-compartment model with first-order absorption kinetics described the observed EFV data adequately. The CYP2B6*6 and ABCB1c.4036A>G genotypes were identified as major factors influencing EFV clearance. The typical estimates of oral clearance, volume of distribution, and absorption rate constant for typical 22 kg children with CYP2B6 *1/*1 and ABCB1c.4036G/G genotypes were 4.3 L/h, 124 L, and 0.776/h, respectively. Clearance was reduced by 28% and 72% in CYP2B6*1/*6 and CYP2B6*6/*6 genotypes, respectively. Compared to week 1, clearance was higher from weeks 8 and 12 in CYP2B6*1/*6 and CYP2B6*1/*1 genotypes, respectively. Simulations indicated that EFV 12-h concentrations were comparable across weight bands, but more than 80% of subjects with CYP2B6*6/*6 had EFV concentrations greater than 4 µg/mL. EFV PK variability among children is partly explained by body weight, treatment duration, CYP2B6*6, and ABCB1 rs3842 genotypes. Therefore, in addition to body weight, pediatric dosing of EFV should consider pharmacogenetic variability, duration of therapy, and individual treatment outcomes.

Impact of Vaccination With the SCB-2019 Coronavirus Disease 2019 Vaccine on Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Household Contact Study in the Philippines.

BACKGROUND: An exploratory household transmission study was nested in SPECTRA, the phase 2/3 efficacy study of the adjuvanted recombinant protein-based COVID-19 vaccine SCB-2019. We compared the occurrence of confirmed COVID-19 infections between households and household contacts of infected SPECTRA placebo or SCB-2019 recipients. METHODS: SPECTRA participants at 8 study sites in the Philippines who developed real-time reverse transcriptase-polymerase chain reaction (rRT-PCR)-confirmed COVID-19 were contacted by a study team blinded to assignment of index cases to vaccine or placebo groups to enroll in this household transmission study. Enrolled households and household contacts were monitored for 3 weeks using rRT-PCR and anti-SARS-CoV-2 N-antigen IgG/IgM testing to detect new COVID-19 infections. RESULTS: One hundred fifty-four eligible COVID-19 index cases (51 vaccinees, 103 placebo) were included. The secondary attack rate per household for symptomatic COVID-19 infection was 0.76% (90% CI: .15-3.90%) if the index case was an SCB-2019 vaccinee compared with 5.88% (90% CI: 3.20-10.8%) for placebo index cases, a relative risk reduction (RRR) of 79% (90% CI: -28% to 97%). The RRR of symptomatic COVID-19 per household member was similar: 84% (90% CI: 28-97%). The impact on attack rates in household members if index cases were symptomatic (n = 130; RRR = 80%; 90% CI: 7-96%) or asymptomatic (n = 24; RRR = 100%; 90% CI: -76% to 100%) was measurable but the low numbers undermine the clinical significance. CONCLUSIONS: In this prospective household contact study vaccination with SCB-2019 reduced SARS-CoV-2 transmission compared with placebo in households and in household members independently of whether or not index cases were symptomatic.

Cost of oral cholera vaccine delivery in a mass immunization program for children in urban Bangladesh.

Cholera poses a substantial health burden in the developing world due to both epidemic and endemic diseases. The World Health Organization recommends oral cholera vaccines for mass vaccination campaigns in addition to traditional prevention practices and treatments in resource-poor settings. In many developing countries like Bangladesh, the major challenge behind implementing mass vaccination campaigns concerns the affordability of the oral cholera vaccine (OCV). Vaccination of children with OCV is not only an impactful approach for controlling cholera at the population level and reducing childhood morbidity but is also considered more cost-effective than vaccinating all ages. The aim of the study was to estimate the cost of an OCV campaign for children from a societal perspective using empirical study. A total of 66,311 children aged 1 to 14 years old were fully vaccinated with two doses of the OCV Shanchol while 9,035 individuals received one dose of this vaccine. The estimated societal cost per individual for full vaccination was US$ 6.11, which includes the cost of vaccine delivery estimated at US$ 1.95. The cost per single dose was estimated at US$ 2.86. The total provider cost for full vaccination was estimated at US$ 6.01 and the recipient cost at US$ 0.10. Our estimation of OCV delivery costs for children was relatively higher than what was found in a similar mass OCV campaign for all age groups, indicating that there may be additional cost factors to consider in targeted vaccine campaigns. This analysis provides useful benchmarks for the possible costs related to delivery of OCV to children and future OCV cost-effectiveness models should factor in these possible cost disparities. Attempts to reduce the cost per dose are likely to have a greater impact on the cost of similar vaccination campaigns in many resource-poor settings.

Differences in diagnosis, management, and outcomes of acute febrile illness by health facility level in southern Ethiopia.

We assessed the diagnosis, management and outcomes of acute febrile illness in a cohort of febrile children aged under 5 years presenting at one urban and two rural health centres and one tertiary hospital between 11 August 2019 and 01 November 2019. Pneumonia was diagnosed in 104 (30.8%) of 338 children at health centres and 128 (65.0%) of 197 at the hospital (p < 0.001). Malaria was detected in 33 (24.3%) of 136 children at the urban health centre, and in 55 (55.6%) of 99 and 7 (7.4%) of 95 children at the rural health centres compared to 11 (11.6%) of 95 at the hospital. Antibacterials were prescribed to 20 (11.5%) of 174 children without guidelines-specified indications (overprescribing) at health centres and in 7 (33.3%) of 21 children at the hospital (p = 0.013). Antimalarials were overprescribed to 13 (7.0%) of 185 children with negative malaria microscopy at the hospital. The fever resolved by day 7 in 326 (99.7%) of 327 children at health centres compared to 177 (93.2%) of 190 at the hospital (p < 0.001). These results suggest that additional guidance to health workers is needed to optimise the use of antimicrobials across all levels of health facilities.

Safety Surveillance of Mass Praziquantel and Albendazole Co-Administration in School Children from Southern Ethiopia: An Active Cohort Event Monitoring.

Preventive chemotherapy (PC) with praziquantel and albendazole co-administration to all at-risk populations is the global intervention strategy to eliminate schistosomiasis and soil-transmitted helminth (STH) from being public health problems. Due to weak pharmacovigilance systems, safety monitoring during a mass drug administration (MDA) is lacking, especially in sub-Saharan Africa. We conducted large-scale active safety surveillance to identify the incidence, types, severity, and associated risk factors of adverse events (AEs) following praziquantel and albendazole MDA in 5848 school children (5−15 years old). Before MDA, 1484 (25.4%) children were prescreened for S. mansoni and STH infections, of whom 71.8% were infected with at least one parasite; 34.5% (512/1484) had S. mansoni and 853 (57.5%) had an STH infection. After collecting the baseline socio-demographic, clinical, and medical data, including any pre-existing clinical symptoms, participants received single dose praziquantel and albendazole MDA. Treatment-associated AEs were actively monitored on days 1 and 7 of the MDA. The events reported before and after the MDA were cross-checked and verified to identify MDA-associated AEs. The cumulative incidence of experiencing at least one type of MDA-associated AE was 13.3% (95% CI = 12.5−14.2%); 85.5%, 12.4%, and 1.8% of reported AEs were mild, moderate, and severe, respectively. The proportion of experiencing one, two, or ≥ three types of AEs was 57.7%, 34.1%, and 8.2%, respectively. The cumulative incidence of AEs in S. mansoni- and (17.0%) and STH (14.1%)-infected children was significantly higher (p < 0.001, χ2 = 15.0) than in non-infected children (8.4%). Headache, abdominal pain, vomiting, dizziness, and nausea were the most common AEs. Being female, older age, having S. mansoni or STH infection were significant predictors of MDA-associated AEs. In summary, praziquantel and albendazole co-administration is generally safe and tolerable. MDA-associated AEs are mostly mild-to-moderately severe and transient. The finding of few severe AEs and significantly high rates of AEs in helminth-infected children underscores the need to integrate pharmacovigilance in MDA programs, especially in high schistosomiasis and STH endemic areas.

Vitamin D binding protein gene polymorphisms are associated with lower plasma 25-hydroxy-cholecalciferol concentrations in Ethiopian lactating women.

Ethiopian women have been reported to have low plasma 25-hydroxy-cholecalciferol (25(OH)D) concentrations despite an abundance of sunshine. Low dietary vitamin D intake, limited skin exposure to sun, and genetics are among factors suggested to affect vitamin D status in this population. In this study (Clinical Trial NCT02210884), we hypothesized that polymorphisms in the vitamin D binding protein (VDBP) gene (rs7041, rs4588) are associated with reduced plasma 25(OH)D concentrations in Ethiopian women. Lactating Ethiopian women (n = 110) were randomly assigned to weekly administration of vitamin D3 (15,000 IU) or a placebo. Plasma 25(OH)D was measured at baseline (within 2 weeks of delivery, before supplementation) and at 3, 6, and 12 months after delivery. Associations between VDBP polymorphism status for rs7041 and rs4588 and plasma 25(OH)D were determined by analysis of variance and multiple linear and logistic regressions. Multiple linear regression with maternal age as a covariate revealed that rs7041 is associated with reduced plasma 25(OH)D (P = .021) and more risk alleles at rs7041 and rs4588 are associated with reduced plasma 25(OH)D (P = .017). Logistic regression models for vitamin D insufficiency showed that additional risk alleles for rs7041 and rs4588 are associated with increased odds ratios (OR = 1.66; 95% CI, 1.10-2.62; P = .019) for plasma 25(OH)D below 40 nmol/L. Supplementation increased plasma 25(OH)D at 3 months in women with fewer risk alleles and across all genotypes at 6 and 12 months. VDBP polymorphisms may contribute to vitamin D insufficiency in Ethiopian lactating women. Furthermore, VDBP polymorphisms may blunt short-term responses to vitamin D supplementation and require longer periods of intervention.