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Inappropriate antimicrobial usage is a key driver of antimicrobial resistance (AMR). Low- and middle-income countries (LMICs) are disproportionately burdened by AMR and young children are especially vulnerable to infections with AMR-bearing pathogens. The impact of antibiotics on the microbiome, selection, persistence, and horizontal spread of AMR genes is insufficiently characterized and understood in children in LMICs. This systematic review aims to collate and evaluate the available literature describing the impact of antibiotics on the infant gut microbiome and resistome in LMICs. In this systematic review, we searched the online databases MEDLINE (1946 to 28 January 2023), EMBASE (1947 to 28 January 2023), SCOPUS (1945 to 29 January 2023), WHO Global Index Medicus (searched up to 29 January 2023), and SciELO (searched up to 29 January 2023). A total of 4,369 articles were retrieved across the databases. Duplicates were removed resulting in 2,748 unique articles. Screening by title and abstract excluded 2,666 articles, 92 articles were assessed based on the full text, and 10 studies met the eligibility criteria that included human studies conducted in LMICs among children below the age of 2 that reported gut microbiome composition and/or resistome composition (AMR genes) following antibiotic usage. The included studies were all randomized control trials (RCTs) and were assessed for risk of bias using the Cochrane risk-of-bias for randomized studies tool. Overall, antibiotics reduced gut microbiome diversity and increased antibiotic-specific resistance gene abundance in antibiotic treatment groups as compared to the placebo. The most widely tested antibiotic was azithromycin that decreased the diversity of the gut microbiome and significantly increased macrolide resistance as early as 5 days posttreatment. A major limitation of this study was paucity of available studies that cover this subject area. Specifically, the range of antibiotics assessed did not include the most commonly used antibiotics in LMIC populations. In this study, we observed that antibiotics significantly reduce the diversity and alter the composition of the infant gut microbiome in LMICs, while concomitantly selecting for resistance genes whose persistence can last for months following treatment. Considerable heterogeneity in study methodology, timing and duration of sampling, and sequencing methodology in currently available research limit insights into antibiotic impacts on the microbiome and resistome in children in LMICs. More research is urgently needed to fill this gap in order to better understand whether antibiotic-driven reductions in microbiome diversity and selection of AMR genes place LMIC children at risk for adverse health outcomes, including infections with AMR-bearing pathogens.

The persistence of healthcare utilization disparities in Ghana despite several policy efforts highlights the urgency of understanding its determinants to enhance equitable health access. We sought to examine the determinants of healthcare utilization in Ghana. We used the 2017 Ghana Living Standard Survey (GLSS) data. This was a cross-sectional design, which employed a stratified two-stage random sampling technique. We analyzed data involving 8,298 respondents with information on visits to healthcare facilities for services on account of illness or injury two weeks prior to the survey. Pearson's chi-squared test was used to assess the distribution of healthcare utilization across background characteristics. Further, we used multivariable Poisson regression model with robust standard error to identify factors independently associated with healthcare utilization. Among the 8,298, the median age was 24 years (interquartile range = 7-47), 45% were males, and 45% had no education. About 42% of respondents utilized health services during an episode of illness or injury. Age, sex, educational level, marital status, wealth quintile, health insurance and severity of illness/injury were independently associated with healthcare utilization. Healthcare utilization increased significantly with wealth quintiles-those in the highest wealth quintiles had about 22% increased utilization compared to those in the lowest wealth quintiles (aPR = 1.22; 95%CI = 1.13-1.32) while it was about 77% higher among those who had valid health insurance compared to those without (aPR = 1.77; 95% CI = 1.68-1.86). Regarding severity of illness or injury, those with severe conditions were about 65% more likely to utilize healthcare services compared to those with acute conditions (aPR = 1.65; 95% CI = 1.53-1.78). Our study underscores the importance of socio-economic factors and health insurance in healthcare utilization in Ghana. Addressing these can pave the way for more equitable access to healthcare services across all segments of the population.

The persistence of healthcare utilization disparities in Ghana despite several policy efforts highlights the urgency of understanding its determinants to enhance equitable health access. We sought to examine the determinants of healthcare utilization in Ghana. We used the 2017 Ghana Living Standard Survey (GLSS) data. This was a cross-sectional design, which employed a stratified two-stage random sampling technique. We analyzed data involving 8,298 respondents with information on visits to healthcare facilities for services on account of illness or injury two weeks prior to the survey. Pearson's chi-squared test was used to assess the distribution of healthcare utilization across background characteristics. Further, we used multivariable Poisson regression model with robust standard error to identify factors independently associated with healthcare utilization. Among the 8,298, the median age was 24 years (interquartile range = 7-47), 45% were males, and 45% had no education. About 42% of respondents utilized health services during an episode of illness or injury. Age, sex, educational level, marital status, wealth quintile, health insurance and severity of illness/injury were independently associated with healthcare utilization. Healthcare utilization increased significantly with wealth quintiles-those in the highest wealth quintiles had about 22% increased utilization compared to those in the lowest wealth quintiles (aPR = 1.22; 95%CI = 1.13-1.32) while it was about 77% higher among those who had valid health insurance compared to those without (aPR = 1.77; 95% CI = 1.68-1.86). Regarding severity of illness or injury, those with severe conditions were about 65% more likely to utilize healthcare services compared to those with acute conditions (aPR = 1.65; 95% CI = 1.53-1.78). Our study underscores the importance of socio-economic factors and health insurance in healthcare utilization in Ghana. Addressing these can pave the way for more equitable access to healthcare services across all segments of the population.

Rotavirus is the most common cause of fatal diarrhoeal disease among children under the age of five globally and is responsible for millions of hospitalizations each year. Although nutritional status and environmental enteric dysfunction (EED) are recognized as important predictors of susceptibility to diarrhoeal disease, no research to date has examined the mechanisms by which undernutrition and EED may protect against prevalence of rotavirus infection. We utilized data collected from a study evaluating the effectiveness of Rotarix™ vaccine against severe gastroenteritis among children under the age of 5 in Zambia. The prevalence of malnutrition, wasting, and stunting at the time of study enrollment was calculated using WHO child growth standards. Commercial ELISA kits were used to assess levels of faecal biomarkers for EED: alpha-1-antitrypsin and myeloperoxidase, and calprotectin. Separate multivariate logistic regression models were used to examine each measure of nutritional status and rotavirus diarrhoea including and excluding adjustment for EED. In models that did not include adjustment for EED, malnourished children had 0.66 times the odds of having rotavirus diarrhoea compared to children with normal nutritional status (95% CI: 0.42, 1.0; p = 0.07). EED severity score was significantly higher among controls asymptomatic for diarrhoeal disease compared to cases with rotavirus diarrhoea (p = 0.02). The morphological changes associated with EED may confer protection against rotavirus infection and subsequent diarrhoeal disease among children. Further research is critically needed to better understand the complex mechanisms by which nutritional status and EED may impact susceptibility to rotavirus in early life.

Sub-Saharan Africa is experiencing an epidemiological transition as the burden of NCDs overtake communicable diseases. However, it is unknown what capacity and gaps exist at primary care level to address the growing burden of NCDs. This study aimed to assess the Zambian health system's capacity to address in NCDs, using an adapted WHO Essential Non Communicable Disease Interventions (WHO PEN) tool. This was a cross-sectional facility survey in the three districts conducted from September 2017 to October 2017. We defined facility readiness along five domains: basic equipment, essential services, diagnostic capacity, counseling services, and essential medicines. For each domain, we calculated an index as the mean score of items expressed as percentage. These indices were compared to an agreed cutoff at 70%, meaning that a facility index or district index below 70% off was considered as 'not ready' to manage NCDs at that level. All analysis were performed using Stata 15 MP. There appeared to be wide heterogeneity between facilities in respect of readiness to manage NCDs. Only 6 (including the three 1st level hospitals) out of the 46 facilities were deemed ready to manage NCDs. Only the first level hospitals scored a mean index higher than the 70% cut off; With regard to medications needed to manage NCDs, urban and rural health facilities were comparably equipped. However, there was evidence that calcium channel blockers (p = 0.013) and insulin (p = 0.022) were more likely to be available in urban and semi-urban health facilities compared to rural facilities. Our study revealed gaps in primary health care capacity to manage NCDs in Zambia, with almost all health facilities failing to reach the minimum threshold. These results could be generalized to other similar districts in Zambia and the sub-region, where health systems remain focused on infectious rather than non-communicable Disease. These results should attract policy attention and potentially form the basis to review current approach to NCD care at the primary care level in Zambia and Sub-Saharan Africa.

Overweight and obesity are major concerns among people living with HIV (PLWH), particularly those on integrase inhibitors, as they elevate the risk of cardiovascular diseases. However, longitudinal data on the burden and risk factors for overweight/obesity in sub-Saharan Africa (SSA) remain limited. This study aimed to estimate the incidence and identify factors associated with overweight and obesity among PLWH who switched to a dolutegravir (DTG)-based ART regimen at Livingstone University Teaching Hospital. We enrolled 249 adults aged [greater than or equal to]18 years living with HIV on ART [non-nucleoside/nucleotide reverse transcriptase inhibitor (NNRTI) n = 174, protease inhibitor (PI) n = 21, and DTG n = 54] with a baseline body mass index (BMI) < 25 kg/m² between April 2019 and May 2020 and conducted a single follow-up assessment between December 2022 and June 2023. Participants were followed for a median of 43 months (interquartile range [IQR]: 42, 44). At follow-up, all participants were on a DTG-based regimen for a median time of 23 months (IQR: 19, 40). Demographic, clinical, and laboratory data were collected using a structured questionnaire. The primary outcome was overweight/obesity, defined as BMI [greater than or equal to] 25 kg/ m.sup.2 . Poisson regression with robust standard errors was used to determine risk factors for being overweight and obesity. The median age was 44 years (interquartile range (IQR) 36, 51) at baseline, with the majority being female (59.4%, n = 148). Over a total follow-up of 871.5 person-years, 44 incident cases of overweight/obesity occurred, yielding a cumulative incidence of 17.7% (44/249) and an incidence rate of 5.05 per 100 person-years. Factors positively associated with the risk of being overweight/obesity included being married (adjusted incidence rate ratio [aIRR] 2.34; 95% CI 1.24, 4.40), lower baseline CD4 count (aIRR 4.13; 95% CI 1.41, 13.38) and higher waist circumference (WC) values (aIRR 1.07; 95% CI 1.03, 1.11). While older age was associated with a lower risk of overweight/obesity (aIRR 0.97; 95% CI 0.94, 0.99). The burden of overweight/obesity was high, and it was significantly driven by demographic, anthropometric, and immunological factors among our study participants. The findings suggest the importance of implementing targeted screening and management strategies for overweight and obesity, particularly among married individuals with higher WC values. Studies investigating the underlying mechanisms of excessive weight gain among PLWH on an integrase inhibitor-based regimen in resource-limited settings are warranted.

Rotavirus is the most common cause of fatal diarrhoeal disease among children under the age of five globally and is responsible for millions of hospitalizations each year. Although nutritional status and environmental enteric dysfunction (EED) are recognized as important predictors of susceptibility to diarrhoeal disease, no research to date has examined the mechanisms by which undernutrition and EED may protect against prevalence of rotavirus infection. We utilized data collected from a study evaluating the effectiveness of Rotarix[TM] vaccine against severe gastroenteritis among children under the age of 5 in Zambia. The prevalence of malnutrition, wasting, and stunting at the time of study enrollment was calculated using WHO child growth standards. Commercial ELISA kits were used to assess levels of faecal biomarkers for EED: alpha-1-antitrypsin and myeloperoxidase, and calprotectin. Separate multivariate logistic regression models were used to examine each measure of nutritional status and rotavirus diarrhoea including and excluding adjustment for EED. In models that did not include adjustment for EED, malnourished children had 0.66 times the odds of having rotavirus diarrhoea compared to children with normal nutritional status (95% CI: 0.42, 1.0; p = 0.07). EED severity score was significantly higher among controls asymptomatic for diarrhoeal disease compared to cases with rotavirus diarrhoea (p = 0.02). The morphological changes associated with EED may confer protection against rotavirus infection and subsequent diarrhoeal disease among children. Further research is critically needed to better understand the complex mechanisms by which nutritional status and EED may impact susceptibility to rotavirus in early life.

Overweight and obesity are major concerns among people living with HIV (PLWH), particularly those on integrase inhibitors, as they elevate the risk of cardiovascular diseases. However, longitudinal data on the burden and risk factors for overweight/obesity in sub-Saharan Africa (SSA) remain limited. This study aimed to estimate the incidence and identify factors associated with overweight and obesity among PLWH who switched to a dolutegravir (DTG)-based ART regimen at Livingstone University Teaching Hospital. We enrolled 249 adults aged ≥18 years living with HIV on ART [non-nucleoside/nucleotide reverse transcriptase inhibitor (NNRTI) n = 174, protease inhibitor (PI) n = 21, and DTG n = 54] with a baseline body mass index (BMI) < 25 kg/m² between April 2019 and May 2020 and conducted a single follow-up assessment between December 2022 and June 2023. Participants were followed for a median of 43 months (interquartile range [IQR]: 42, 44). At follow-up, all participants were on a DTG-based regimen for a median time of 23 months (IQR: 19, 40). Demographic, clinical, and laboratory data were collected using a structured questionnaire. The primary outcome was overweight/obesity, defined as BMI ≥ 25 kg/ m2. Poisson regression with robust standard errors was used to determine risk factors for being overweight and obesity. The median age was 44 years (interquartile range (IQR) 36, 51) at baseline, with the majority being female (59.4%, n = 148). Over a total follow-up of 871.5 person-years, 44 incident cases of overweight/obesity occurred, yielding a cumulative incidence of 17.7% (44/249) and an incidence rate of 5.05 per 100 person-years. Factors positively associated with the risk of being overweight/obesity included being married (adjusted incidence rate ratio [aIRR] 2.34; 95% CI 1.24, 4.40), lower baseline CD4 count (aIRR 4.13; 95% CI 1.41, 13.38) and higher waist circumference (WC) values (aIRR 1.07; 95% CI 1.03, 1.11). While older age was associated with a lower risk of overweight/obesity (aIRR 0.97; 95% CI 0.94, 0.99). The burden of overweight/obesity was high, and it was significantly driven by demographic, anthropometric, and immunological factors among our study participants. The findings suggest the importance of implementing targeted screening and management strategies for overweight and obesity, particularly among married individuals with higher WC values. Studies investigating the underlying mechanisms of excessive weight gain among PLWH on an integrase inhibitor-based regimen in resource-limited settings are warranted.

Background Seroprevalence estimates of endemic human coronaviruses (HCoV) and novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited in Zambia. Information on development of acquired immunity to endemic HCoV in early life is also scarce and the potential cross-protective effect of HCoV immunity on SARS-CoV-2 remains debatable. We investigated seroprevalence of endemic HCoV in mother-child dyads and SARS-CoV-2 in children and explored the association between HCoV and SARS-CoV-2 antibodies in children to elucidate coronavirus seroepidemiology in Zambia. Methods We measured endemic HCoV NL63, 229E, OC43 and HKU1 and SARS-CoV-2 Spike protein subunit 1 (S1) specific immunoglobulin G (IgG) using an immunoassay. We tested plasma samples collected from Zambian mother-child dyads before the coronavirus disease 2019 pandemic in 2018 and 2019, and during the pandemic in 2020 and 2021. We determined HCoV S1 IgG seropositivity in mothers and children and SARS-CoV-2 S1 IgG seropositivity in children. We correlated HCoV antibodies in the mother-child pairs and longitudinally profiled HCoV antibodies in children to investigate development of HCoV immunity and contribution of maternal immunity. We compared child HCoV S1 IgG and SARS-CoV-2 S1 IgG antibodies before and during the pandemic to explore cross-reactivity. Results HCoV and SARS-CoV-2 S1 IgG antibodies were detected among mothers and children. Child HCoV seroconversion occurred following waning of maternal immunity but there was no significant correlation between HCoV and SARS-CoV-2 S1 IgG before and during the pandemic. A rise in SARS-CoV-2 S1 IgG seroprevalence among children was observed following the second and third epidemic waves of the COVID-19 pandemic in Zambia. Conclusions Endemic HCoV NL63, 229E, OC43 and HKU1 widely circulated and are acquired early in Zambia. SARS-CoV-2 seroprevalence in children speaks to the susceptibility of this population to infection that necessitates their inclusion in control measures.

HIV self-testing (HIVST) is a novel approach designed to assist in achieving the goal of at least 90% of the population that learn their HIV status. A self-test user with a positive test is required to visit a clinic to link into HIV care, yet little is known about patient preferences for linkage strategies. We examined the intention to link to care amongst potential HIVST users and the suitability of three linkage to care strategies in Lusaka Province, Zambia. We conducted a representative cross sectional survey of 1,617 individuals aged 16-49 years old in Lusaka Province. Participants were shown a video of the HIVST. Data on intention to link to care and preferred linkage to care strategies-text message, phone call and home visits were collected. Eight focus group discussions were held concurrently with survey respondents to understand their preferences between the three linkage to care strategies. Of 1617 enrolled, 60% were women, 40% were men, with an average age of 27years (IQR = 22, 35). More men than women had at least secondary education (84% vs 77%) and were either employed or self-employed (67% vs. 41%). 85% (95%CI = 83 to 86) of participants said they would link to care within the first week of a positive self-test. Income >2,000 Kwacha (USD 200) per month versus income < 2,000 Kwacha (Adjusted odds ratio (AOR) = 0.59; 95%CI: 0.40 to 0.88; p = 0.009) and never versus prior HIV testers (AOR = 0.54; 95%CI: 0.32 to 0.91; p = 0.020) were associated with reduced odds of intention to link to care. 53% (95%CI = 50 to 55) preferred being prompted to link to care by home visits compared to phone call (30%) or SMS (17%). We found almost nine out of ten potential HIVST users in the general population intend to link to care shortly after a positive test, and preferred home visits or phone calls to facilitate linkage, rather than SMS. Also, higher income earners and those who never tested for HIV were associated with reduced odds of intention to link to care. Policy guidelines and implementation strategies for HIVST should be responsive to patient preferences for linkage to care strategies to achieve the continuum of HIV care.