Human cytomegalovirus seropositivity and its influence on oral rotavirus vaccine immunogenicity: a specific concern for HIV-exposed-uninfected infants.

Oral rotavirus vaccines demonstrate diminished immunogenicity in low-income settings where human cytomegalovirus infection is acquired early in childhood and modulates immunity. We hypothesized that human cytomegalovirus infection around the time of vaccination may influence immunogenicity. We measured plasma human cytomegalovirus-specific immunoglobulin M antibodies in rotavirus vaccinated infants from 6 weeks to 12 months old and compared rotavirus immunoglobulin A antibody titers between human cytomegalovirus seropositive and seronegative infants. There was no evidence of an association between human cytomegalovirus serostatus at 9 months and rotavirus-specific antibody titers at 12 months (geometric mean ratio 1.01, 95% CI: 0.70, 1.45; P = 0.976) or fold-increase in RV-IgA titer between 9 and 12 months (risk ratio 0.999, 95%CI: 0.66, 1.52; P = 0.995) overall. However, HIV-exposed-uninfected infants who were seropositive for human cytomegalovirus at 9 months old had a 63% reduction in rotavirus antibody geometric mean titers at 12 months compared to HIV-exposed-uninfected infants who were seronegative for human cytomegalovirus (geometric mean ratio 0.37, 95% CI: 0.17, 0.77; P = 0.008). While the broader implications of human cytomegalovirus infections on oral rotavirus vaccine response might be limited in the general infant population, the potential impact in the HIV-exposed-uninfected infants cannot be overlooked. This study highlights the complexity of immunological responses and the need for targeted interventions to ensure oral rotavirus vaccine efficacy, especially in vulnerable subpopulations.

Clinic-based evaluation of point-of-care dual HIV/syphilis rapid diagnostic tests at primary healthcare antenatal facilities in South Africa and Zambia.

BACKGROUND: Southern African countries have the largest global burden of HIV and syphilis, with a high prevalence among women of reproductive age. Although antenatal screening is standard of care, syphilis screening has generally lagged behind HIV screening. We aimed to evaluate the performance and operational characteristics of two commercial dual HIV/syphilis point-of-care tests (POCTs) for simultaneous maternal HIV/syphilis screening. METHODS: A clinic-based evaluation of dual HIV/syphilis POCTs (SD Bioline and Chembio) was conducted at five primary healthcare centres (PHCs) in South Africa and Zambia. POCT results using capillary fingerprick blood were compared to reference laboratory syphilis and HIV serological assays. RESULTS: Three thousand four hundred twelve consenting pregnant women aged ≥ 18 years were enrolled. The prevalence of treponemal antibody seropositivity and HIV infection ranged from 3.7 to 9.9% (n = 253) and 17.8 to 21.3% (n = 643), respectively. Pooled sensitivity for syphilis compared to the reference assay was 66.0% (95%CI 57.7-73.4) with SD Bioline and 67.9% (95%CI 58.2-76.3) with Chembio. Pooled specificity for syphilis was above 98% with both POCTs. The sensitivities of SD Bioline and Chembio assays were 78.0% (95%CI 68.6-85.7) and 81.0% (95%CI 71.9-88.2), respectively compared to an active syphilis case definition of treponemal test positive with a rapid plasma reagin titre of ≥ 8. The negative predictive values (NPVs) based on various prevalence estimates for syphilis with both assays ranged from 97 to 99%. The pooled sensitivity for HIV was 92.1% (95%CI 89.4-94.2) with SD Bioline; and 91.5% (95%CI 88.2-93.9) with Chembio. The pooled specificities for HIV were 97.2% (95%CI 94.8-98.5) with SD Bioline and 96.7% (95%CI 95.1-97.8) with Chembio. The NPV based on various prevalence estimates for HIV with both assays was approximately 98%. Most participating women (91%) preferred dual POCTs over two single POCTs for HIV and syphilis, and healthcare providers gave favourable feedback on the utility of both assays at PHC level. CONCLUSIONS: Based on the need to improve antenatal screening coverage for syphilis, dual HIV/syphilis POCTs could be effectively incorporated into antenatal testing algorithms to enhance efforts towards elimination of mother-to-child transmission of these infections.

Long-term hepatitis B and liver outcomes among adults taking tenofovir-containing antiretroviral therapy for HBV/HIV coinfection in Zambia.

BACKGROUND: Long-term outcomes of tenofovir-containing antiretroviral therapy (ART) for HBV/HIV coinfection were evaluated in Zambia. METHODS: A prospective cohort of adults with HIV and hepatitis B surface antigen (HBsAg)-positivity was enrolled at ART (included tenofovir DF + lamivudine) initiation. On therapy, we ascertained HBV viral load (VL) non-suppression, ALT elevation, serologic end-points, progression of liver fibrosis, based on elastography, and hepatocellular carcinoma (HCC) incidence. We also described a subgroup (low HBV VL and no/minimal fibrosis at baseline) that, under current international guidelines, would not have been treated in the absence of their HIV infection. RESULTS: Among 289 participants, at ART start, median age was 34 years, 40·1% were women, median CD4 count was 191 cells/mm3, 44·2% were hepatitis B e antigen-positive, and 28·4% had liver fibrosis/cirrhosis. Over median 5.91 years of ART, 13·6% developed HBV viral non-suppression, which was associated with advanced HIV disease. ALT elevation on ART was linked with HBV VL non-suppression. Regression of fibrosis and cirrhosis were common, progression to cirrhosis was absent, and no cases of HCC were ascertained. HBsAg seroclearance was 9·4% at 2 and 15·4% at 5 years, with higher rates among patients with low baseline HBV replication markers. DISCUSSION: Reassuring long-term liver outcomes were ascertained during tenofovir-based ART for HBV/HIV coinfection in Zambia. Higher than expected HBsAg seroclearance during ART underscores the need to include people with HIV in HBV cure research.

Impact of antibiotics on gut microbiome composition and resistome in the first years of life in low- to middle-income countries: A systematic review.

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSION: 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.

Intersection of alcohol use, HIV infection, and the HIV care continuum in Zambia: nationally representative survey.

Through a nationally-representative household survey, we measured the prevalence and correlates of unhealthy alcohol use (UAU) in Zambia and its association with the HIV care continuum. Adolescent and adult (ages 15-59 years) data, including the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), from the 2016 Zambia Population-based HIV Impact Assessment, were analyzed. UAU was defined as AUDIT-C of 3 + points for women and 4 + for men. Among 20,923 participants, 15.3% had UAU; this was 21.6% among people living with HIV (PLWH). Male sex, increasing age, being employed, urban residence, and having HIV were independent correlates of UAU (all P < 0.05). Among PLWH, UAU was associated with reduced HIV diagnosis (adjusted odds ratio [AOR]: 0.66, 95% CI 0.50-0.88) and non-significant trends toward reduced ART use if diagnosed (AOR: 0.73, 95% CI 0.73-1.10) and reduced viral suppression (VS) if on ART (AOR: 0.91, 95% CI 0.57-1.44). Overall, UAU was linked to 25% lower odds of VS compared to abstinence. UAU in Zambia disproportionately affects certain groups including PLWH. Achieving and sustaining HIV epidemic control in Zambia will require evidence-based approaches to screen and treat UAU.

Associations of inter-annual rainfall decreases with subsequent HIV outcomes for persons with HIV on antiretroviral therapy in Southern Africa: a collaborative analysis of cohort studies.

BACKGROUND: Periods of droughts can lead to decreased food security, and altered behaviours, potentially affecting outcomes on antiretroviral therapy (ART) among persons with HIV (PWH). We investigated whether decreased rainfall is associated with adverse outcomes among PWH on ART in Southern Africa. METHODS: Data were combined from 11 clinical cohorts of PWH in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, participating in the International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration. Adult PWH who had started ART prior to 01/06/2016 and were in follow-up in the year prior to 01/06/2016 were included. Two-year rainfall from June 2014 to May 2016 at the location of each HIV centre was summed and ranked against historical 2-year rainfall amounts (1981-2016) to give an empirical relative percentile rainfall estimate. The IeDEA-SA and rainfall data were combined using each HIV centre's latitude/longitude. In individual-level analyses, multivariable Cox or generalized estimating equation regression models (GEEs) assessed associations between decreased rainfall versus historical levels and four separate outcomes (mortality, CD4 counts < 200 cells/mm3, viral loads > 400 copies/mL, and > 12-month gaps in follow-up) in the two years following the rainfall period. GEEs were used to investigate the association between relative rainfall and monthly numbers of unique visitors per HIV centre. RESULTS: Among 270,708 PWH across 386 HIV centres (67% female, median age 39 [IQR: 32-46]), lower rainfall than usual was associated with higher mortality (adjusted Hazard Ratio: 1.18 [95%CI: 1.07-1.32] per 10 percentile rainfall rank decrease) and unsuppressed viral loads (adjusted Odds Ratio: 1.05 [1.01-1.09]). Levels of rainfall were not strongly associated with CD4 counts < 200 cell/mm3 or > 12-month gaps in care. HIV centres in areas with less rainfall than usual had lower numbers of PWH visiting them (adjusted Rate Ratio: 0.80 [0.66-0.98] per 10 percentile rainfall rank decrease). CONCLUSIONS: Decreased rainfall could negatively impact on HIV treatment behaviours and outcomes. Further research is needed to explore the reasons for these effects. Interventions to mitigate the health impact of severe weather events are required.

Development and validation of a novel scale for antiretroviral therapy readiness among pregnant women in urban Zambia with newly diagnosed HIV infection.

BACKGROUND: Women who are newly diagnosed with HIV infection during pregnancy may not be ready to immediately initiate lifelong antiretroviral therapy (ART; called Option B +) as is recommended. Lack of "readiness" drives early disengagement from care and undermines prevention of HIV transmission to infants. Several studies have shown high early attrition of women initiating ART in pregnancy. Although poor ART uptake and adherence have been attributed to various factors including stigma, disclosure issues and structural issues, there is no standard way of determining which pregnant woman will face challenges and therefore need additional support. We developed and validated a novel ART readiness tool in Lusaka, Zambia. METHODS: The aim of this study was to develop and validate a tool that could be used to assess how ready a newly diagnosed pregnant woman living with HIV would be to initiate ART on the day of diagnosis. Using a mixed method design, we conducted this study in three public-setting health facilities in Lusaka, Zambia. Informed by qualitative research and literature review, we identified 27 candidate items. We assessed content validity using expert and target population judgment approaches. We administered the 27-item questionnaire to 454 newly diagnosed pregnant women living with HIV, who were enrolled into a randomized trial (trials number NCT02459678). We performed item reduction analysis and used Cronbach's alpha coefficient of 0.70 as threshold for reliability. RESULTS: A total of 454 pregnant women living with HIV enrolled in the study between March 2017 and December 2017; 452 had complete data for analysis. The correlation coefficient between the 27 items on the completed ART readiness scale ranged from 0.31 to 0.70 while item discrimination index ranged from -0.01 to 2.38. Sixteen items were selected for the final scale, representing three domains, which we classified as "internalized and anticipated HIV stigma", "partner support" and "anticipated structural barriers". CONCLUSION: We developed and validated a tool that could be used to assess readiness of newly diagnosed women living with HIV to initiate ART. This ART readiness tool could allow clinics to tailor limited resources to pregnant women living with HIV needing additional support to initiate and remain on ART.

Burden of chronic kidney diseases and underlying causes in Zambia: evidence from the global burden of disease study 2019.

INTRODUCTION: Chronic kidney disease (CKD) has been a global public health problem and a major source of suffering and poor quality of life for those afflicted. Using data from the global burden of disease (GBD) study 2019, we estimated the magnitude of the burden of CKD as well as the underlying causes of CKD in the Zambian population. METHOD: The data used for this study were extracted from the GBD 2019 study. The GBD 2019 provides estimates of several metrics of disease burden including the commonly used disability-adjusted life year (DALYs) for over 369 diseases and injuries, and 87 risk factors and combinations of these in 204 countries and territories from 1990 to 2019. We estimated the burden of CKD as the number and rates (per 100,000 population) of DALYs, disaggregated by year, sex, and age group. We examined the underlying causes of CKD by estimating the population attributable fraction as the percentage contributions of risk factors to CKD DALY. RESULTS: The number of DALYs for CKD was estimated as 76.03 million (95% UI: 61.01 to 93.36) in 2019 compared to 39.42 million (95% UI: 33.09 to 45.90) in 1990, representing 93% increase whereas the DALYs rate per 100,000 population was estimated as 416.89 (95% UI: 334.53 to 511.93) in 2019 compared to 496.38 (95% UI: 416.55 to 577.87) in 1990, representing 16% reduction. CKD due to hypertension accounted for 18.7% of CKD DALYs and CKD due to diabetes (types 1 and 2) accounted for 22.7%, while CKD from glomerulonephritis accounted for the most DALYs at 33%. The age group most impacted from CKD were adolescents and young adults. CONCLUSION: The burden of CKD remains high in the Zambian population with diabetes, high blood pressure, and glomerulonephritis as important causes. The results highlight the need to develop a comprehensive action plan to prevent and treat kidney disease. Increasing the awareness of CKD among the public as well as adaptation of guidelines for treating patients with end stage kidney disease are important considerations.

Assessment of the influence of ABO blood groups on oral cholera vaccine immunogenicity in a cholera endemic area in Zambia.

BACKGROUND: Histo-blood group antigens (HBGAs) which include the ABO and Lewis antigen systems have been known for determining predisposition to infections. For instance, blood group O individuals have a higher risk of severe illness due to V. cholerae compared to those with non-blood group O antigens. We set out to determine the influence that these HBGAs have on oral cholera vaccine immunogenicity and seroconversion in individuals residing within a cholera endemic area in Zambia. METHODOLOGY: We conducted a longitudinal study nested under a clinical trial in which samples from a cohort of 223 adults who were vaccinated with two doses of Shanchol™ and followed up over 4 years were used. We measured serum vibriocidal geometric mean titers (GMTs) at Baseline, Day 28, Months 6, 12, 24, 30, 36 and 48 in response to the vaccine. Saliva obtained at 1 year post vaccination was tested for HBGA phenotypes and secretor status using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Of the 133/223 participants included in the final analysis, the majority were above 34 years old (58%) and of these, 90% were males. Seroconversion rates to V. cholerae O1 Inaba with non-O (23%) and O (30%) blood types were comparable. The same pattern was observed against O1 Ogawa serotype between non-O (25%) and O (35%). This trend continued over the four-year follow-up period. Similarly, no significant differences were observed in seroconversion rates between the non-secretors (26%) and secretors (36%) against V. cholerae O1 Inaba. The same was observed for O1 Ogawa in non-secretors (22%) and the secretors (36%). CONCLUSION: Our results do not support the idea that ABO blood grouping influence vaccine uptake and responses against cholera.

Impact of insecticide-treated nets and indoor residual spraying on self-reported malaria prevalence among women of reproductive age in Ghana: implication for malaria control and elimination.

BACKGROUND: The Global Fund alone contributed 56% of all international financing for malaria and has invested more than US$13.5 billion in malaria treatment, prevention, and control programmes by June 2021. These investments include interventions such as mosquito nets, indoor residual spraying, and preventive treatment for children and pregnant women. However, there is paucity of studies for assessment of such investments to a reduction in malaria prevalence. This study was aimed at quantifying the impact of household access to insecticide-treated nets (ITNs) and the indoor residual spraying (IRS) on self-reported malaria prevalence among women of reproductive age in Ghana. METHODS: The study analysed the 2016 Ghana Malaria Indicator Survey (MIS) data. The MIS is a nationwide survey that included women aged 15-49 years. Poisson regression model with inverse probability to treatment weighting was used to determine average treatment effect estimate of the two malaria interventions on self-reported malaria prevalence among women of reproductive age in Ghana. RESULTS: A total sample of 4861 women interviewed from the 2016 Ghana MIS was used for analysis. The prevalence of self-reported malaria in 2016 was 34.4% (95% CI [32.4%, 36.4%]). Approximately 80.0% of women lived in households with access to ITNs [Percentage (Pr) = 79.9%, (95% CI [78.0%, 81.7%])], 12.4% (95% CI [7.5%, 19.8%]) of the households had access to IRS and 11.4% (95% CI [7.0%, 18.0%]) of the households had access to both ITNs and IRS. Household access to only ITN contributed to 7.1 percentage point (pt) reduction in the self-reported malaria among women (95% CI [- 12.0%, - 2.1%], p = 0.005) whilst IRS at the households contributed to 6.8pt reduction in malaria prevalence (95% CI [- 12.0%, - 2.1%], p = 0.005). Households with access to both ITNs and IRS contributed to a 27.1pt reduction in self-reported malaria prevalence among women (95% CI [- 12.0%, - 2.1%], p = 0.005). CONCLUSION: Access to both ITNs and application of IRS at the household level contributed to a significant reduction in self-reported malaria prevalence among women of reproductive age in Ghana. This finding confirms the need for integration of malaria control interventions to facilitate attainment of malaria elimination in Ghana.

Efficacy of the Common Elements Treatment Approach (CETA) for Unhealthy Alcohol Use Among Adults with HIV in Zambia: Results from a Pilot Randomized Controlled Trial.

This randomized controlled trial tested the efficacy of a multi-session, evidence-based, lay counselor-delivered transdiagnostic therapy, the Common Elements Treatment Approach (CETA), in reducing unhealthy alcohol use and comorbidities among persons living with HIV (PLWH) in Zambia. Adult PLWH with (a) unhealthy alcohol use plus mental health or substance use comorbidities, or (b) severe unhealthy alcohol use were randomized to receive a single-session alcohol brief intervention (BI) alone or BI plus referral to CETA. Outcomes were measured at baseline and a 6-month follow-up and included Alcohol Use Disorders Identification Test (AUDIT) score (primary), depression and trauma symptoms, and other substance use (secondary). We enrolled 160 participants; 78 were randomized to BI alone and 82 to BI plus CETA. Due to COVID-19, the trial ended early before 36 participants completed. Statistically and clinically significant reductions in mean AUDIT score from baseline to 6-month follow-up were observed in both groups, however, participants assigned to BI plus CETA had significantly greater reductions compared to BI alone (- 3.2, 95% CI - 6.2 to - 0.1; Cohen's d: 0.48). The CETA effect size for AUDIT score increased in line with increasing mental health/substance use comorbidity (0 comorbidities d = 0.25; 1-2 comorbidities d = 0.36; 3+ comorbidities d = 1.6). Significant CETA treatment effects were observed for depression, trauma, and several other substances. BI plus referral to CETA was feasible and superior to BI alone for unhealthy alcohol use among adults with HIV, particularly among those with comorbidities. Findings support future effectiveness testing of CETA for HIV outcomes among PLWH with unhealthy alcohol use.Clinical Trials Number: NCT03966885.

Estimated incidence and transmission intensity of rubella infection in Zambia pre-vaccine era 2005-2016.

The rubella disease burden in Zambia may be under-estimated. Using models, we describe the transmission dynamics, determine the incidence estimates and assess the level of underestimation of the real burden of rubella infection in Zambia during the pre-vaccination period 2005-2016. This study used both the deterministic compartmental model and likelihood-based method using a Bayesian framework to describe the epidemiology of rubella. A total of 1313 cases of rubella were confirmed with the highest annual number of 255 new cases recorded in 2008. However, 2014 recorded the highest monthly median positivity rate of 9.0%. The observed median rubella cases were 5.5. There was a seasonal pattern in the occurrence of laboratory-confirmed rubella, with higher test positivity rates of rubella infection usually recorded in the months of September, October and November. The modelled monthly median incidence of rubella infection among the general population was 76 and 20 among pregnant women. The incidence of rubella among the non-pregnant women was 44. The average effective reproductive number (Rt) between 2005 and 2016 was estimated as 1.2 with the peak of infection occurring in 2016. The measles surveillance system underestimates the observed burden of rubella. A mass vaccination campaign conducted between January and July is recommended.

Effect of Enhanced Adherence Package on Early ART Uptake Among HIV-Positive Pregnant Women in Zambia: An Individual Randomized Controlled Trial.

We evaluated the effect of an option B-plus Enhanced Adherence Package (BEAP), on early ART uptake in a randomized controlled trial. HIV-positive, ART naïve pregnant women in Lusaka, Zambia, were randomized to receive BEAP (phone calls/home visits, additional counseling, male partner engagement and missed-visit follow-up) versus standard of care (SOC). The primary outcome was initiating and remaining on ART at 30 days. Analysis was by intention to treat (ITT) using logistic regression. Additional per protocol analysis was done. We enrolled 454 women; 229 randomized to BEAP and 225 to SOC. Within 30 days of eligibility, 445 (98.2%) initiated ART. In ITT analysis, 82.5% BEAP versus 80.4% SOC participants reached primary outcome (crude relative risk [RR] 1.03; 95% confidence interval [CI] 0.91-1.16; Wald test statistic = 0.44; p-value = 0.66). In per protocol analysis, (92 participants (40.2%) excluded), 91.9% BEAP versus 80.4% SOC participants reached primary outcome (crude RR 1.14; 95% CI 1.02-1.29; Wald test statistic = 2.23; p-value = 0.03). Early ART initiation in pregnancy was nearly universal but there was early drop out suggesting need for additional adherence support.This trial was registered at ClinicalTrials.gov (trials number NCT02459678) on May 14, 2015.

Prescribing patterns and compliance with World Health Organization recommendations for the management of severe malaria: a modified cohort event monitoring study in public health facilities in Ghana and Uganda.

BACKGROUND: Injectable artesunate (AS) is the World Health Organization (WHO) recommended medication for the treatment of severe malaria followed with an oral artemisinin-based combination therapy (ACT). There are few studies indicating how physicians prescribe injectable AS, injectable quinine (Q) or injectable artemether (AR) and ACT for severe malaria. This study was undertaken to evaluate prescription compliance to the WHO recommendation in 8 public health facilities in Ghana and Uganda. This was a modified cohort event monitoring study involving patients who were administered with injectable anti-malarial for treatment of presumed or confirmed severe malaria. Patients prescribed at least one dose of injectable artesunate, artemether or quinine qualified to enrol in the study. Patients were recruited at inpatient facilities and followed up in the hospital, by phone or at home. Following WHO recommendations, patients are to be prescribed 3 doses of injectable AS, Q or AR for at least 24 h followed with oral ACT. Compliance rate was estimated as the number of patient prescriptions that met the WHO recommendation for treatment of severe malaria divided by the total number of patients who completed the study by end of follow up. Log-binomial regression model was used to identify predictors for compliance. Based on the literature and limitations of available data from the patients' record, the diagnosis results, age, gender, weight, and country were considered as potential predictors of prescriber adherence to the WHO recommendations. RESULTS: A total of 1191 patients completed the study, of which 93% were prescribed injectable AS, 3.1% (injectable AR or Q) with 32.5% prescribed follow-on oral ACT and 26% on concomitant antibiotics. 391 (32.8%) were in Ghana and 800 (67.2%) in Uganda. There were 582 (48.9%) women. The median age was 3.9 years (IQR = 2, 9) and median weight was 13 kg (IQR = 10, 20). Of the 1191 patients, 329 of the prescriptions complied with the WHO recommendation (compliance rate = 27.6%; 95% CI = [25.2, 30.2]). Diagnostic results (Adjusted prevalence ratio (aPR) = 4.56; 95% = [3.42, 6.08]; p < 0.0001) and weight (20 + kg vs < 10 kg: aPR = 0.65; 95% = [0.44, 0.96]; p = 0.015) were identified as factors independently associated with compliance. CONCLUSION: Injectable AS is the most commonly prescribed medicine in the management of severe malaria in Ghana and Uganda. However, adherence to the WHO recommendation of at least 3 doses of injectable anti-malarial in 24 h followed by a full course of ACT is low, at less than 30%.

Early linear growth retardation: results of a prospective study of Zambian infants.

BACKGROUND: Linear growth retardation is the most dominant nutritional problem globally. We aimed to describe linear growth trajectory among infants under 2 years of age using the WHO growth velocity standards. METHOD: This was a prospective cohort study of infants enrolled at 6 weeks of age and followed up for up to 24 months in Kamwala Urban Health Centre, Lusaka, Zambia. The study was conducted between April 2013 and March 2015. Infants were enrolled if they were 6-12 weeks of age and the mother was willing to participate voluntarily and provided informed consent. Anthropometric data were collected at scheduled clinic visits at 1 month, 2 months, 3 months, then quarterly until the infant was 24 months old. We defined linear growth velocity as the rate of change in height. We estimated linear growth velocity as the first derivative of the penalized cubic spline mixed effects model. RESULTS: A total of 338 children were included in the analysis. Of these, 185 (54.7%) were female, 115 (34.1%) were born to HIV positive mothers and thus classified as HIV Exposed (HE). The mean age of children at enrollment was 1.6 months (SD = 0.15). On average, the growth velocity for 3-month length increments conditional on age were 0-3 months = 2.97 cm/3mo (95%CI = 2.69, 3.25); 3-6 months = 2.62 cm/3mo (95%CI = 2.38, 2.87); 6-9 months = 1.57 cm/3mo (95%CI = 1.43, 1.71); 9-12 months = 1.18 cm/3mo (95%CI = 1.08, 1.28); 12-15 month = 1.14 cm/3mo (95%CI = 1.02, 1.27); 15-18 months = 0.87 cm/3mo (95%CI = 0.79, 0.96); 18-21 months = 0.80 cm/3mo (95%CI = 0.72, 0.89); and 21-24 months = 0.86 cm/3mo (95%CI = 0.77, 0.96). For both boys and girls, the growth velocity in our cohort were consistently below the 3rd percentile of the WHO linear growth velocity standard. The estimated mean height and the age at which growth begins to falter were 68.6 cm (95%CI = 68.0, 69.2) and 13.6 months (95%CI = 13.2, 14.1) respectively. CONCLUSION: We found slower rate of growth among otherwise healthy Zambian infants. The data suggests that growth retardation is universal and profound in this cohort and may have already been occurring in utero.

The prevalence of submicroscopic Plasmodium falciparum gametocyte carriage and multiplicity of infection in children, pregnant women and adults in a low malaria transmission area in Southern Ghana.

BACKGROUND: The gametocyte stage of Plasmodium falciparum is considered an important target for disrupting malaria transmission. Indications are that various demographic groups, such as children and pregnant women may differ in risk of harbouring gametocytes, which may be crucial for targeted control. In this study, the relationship between the prevalence and multiplicity of P. falciparum, asexual parasite infections and gametocytaemia was assessed in three different demographic groups in an area of southern Ghana with low malaria endemicity. Levels of antibody responses to Pfs230 were also assessed as a proxy for the presence of gametocytes. METHODS: The study involved multiple cross-sectional sampling of children (N = 184, aged 2-15 years), male and non-pregnant female adults (N = 154, aged 16-65 years) and pregnant women (N = 125, aged 18-45 years) from Asutsuare in the Shai Osudoku District of Greater Accra Region in Ghana. Asexual parasitaemia was detected by microscopy and PCR, and gametocytaemia was assessed by Pfs25-real time PCR. Multiclonal P. falciparum infections were estimated by msp2 genotyping and an indirect ELISA was used to measure plasma IgG antibodies to Pfs230 antigen. RESULTS: Overall, children and pregnant women had higher prevalence of submicroscopic gametocytes (39.5% and 29.7%, respectively) compared to adults (17.4%). Multiplicity of infection observed amongst children (3.1) and pregnant women (3.9) were found to be significantly higher (P = 0.006) compared with adults (2.7). Risk of gametocyte carriage was higher in individuals infected with P. falciparum having both Pfmsp2 3D7 and FC27 parasite types (OR = 5.92, 95% CI 1.56-22.54, P = 0.009) compared with those infected with only 3D7 or FC27 parasite types. In agreement with the parasite prevalence data, anti-Pfs230 antibody levels were lower in gametocyte positive adults (ß = - 0.57, 95% CI - 0.81, - 0.34, P < 0.001) compared to children. CONCLUSIONS: These findings suggest that children and pregnant women are particularly important as P. falciparum submicroscopic gametocyte reservoirs and represent important focus groups for control interventions. The number of clones increased in individuals carrying gametocytes compared to those who did not carry gametocytes. The higher anti-gametocyte antibody levels in children suggests recent exposure and may be a marker of gametocyte carriage.

Hypertension management in rural primary care facilities in Zambia: a mixed methods study.

BACKGROUND: Improved primary health care is needed in developing countries to effectively manage the growing burden of hypertension. Our objective was to evaluate hypertension management in Zambian rural primary care clinics using process and outcome indicators to assess the screening, monitoring, treatment and control of high blood pressure. METHODS: Better Health Outcomes through Mentoring and Assessment (BHOMA) is a 5-year, randomized stepped-wedge trial of improved clinical service delivery underway in 46 rural Zambian clinics. Clinical data were collected as part of routine patient care from an electronic medical record system, and reviewed for site performance over time according to hypertension related indicators: screening (blood pressure measurement), management (recorded diagnosis, physical exam or urinalysis), treatment (on medication), and control. Quantitative data was used to develop guides for qualitative in-depth interviews, conducted with health care providers at a proportional sample of half (20) of clinics. Qualitative data was iteratively analyzed for thematic content. RESULTS: From January 2011 to December 2014, 318,380 visits to 46 primary care clinics by adults aged ≥ 25 years with blood pressure measurements were included. Blood pressure measurement at vital sign screening was initially high at 89.1% overall (range: 70.1-100%), but decreased to 62.1% (range: 0-100%) by 48 months after intervention start. The majority of hypertensive patients made only one visit to the clinics (57.8%). Out of 9022 patients with at least two visits with an elevated blood pressure, only 49.3% had a chart recorded hypertension diagnosis. Process indicators for monitoring hypertension were <10% and did not improve with time. In in-depth interviews, antihypertensive medication shortages were common, with 15/20 clinics reporting hydrochlorothiazide-amiloride stockouts. Principal challenges in hypertension management included 1) equipment and personnel shortages, 2) provider belief that multiple visits were needed before official management, 3) medication stock-outs, leading to improper prescriptions and 4) poor patient visit attendance. CONCLUSIONS: Our findings suggest that numerous barriers stand in the way of hypertension diagnosis and management in Zambian primary health facilities. Future work should focus on performance indicator development and validation in low resource contexts, to facilitate regular and systematic data review to improve patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier NCT01942278 . Date of Registration: September 2013.

Predictors of quality of life in patients with diabetes mellitus in two tertiary health institutions in Ghana and Nigeria.

BACKGROUND: Patients with chronic diseases such as Type 2 diabetes mellitus (DM) usually have a relatively poor quality of life (QoL), because the cost of care (living expenses and health) or diet restrictions are heavily felt by these patients, and this is of a public health concern. However, limited data on DM QoL exist in Ghana and Nigeria. This makes it imperative for data to be collated in that regard. MATERIALS AND METHODS: We adopted the Strengthening The reporting of observational studies in epidemiology (STROBE) consensus checklist to survey the patients with DM seen at the diabetic clinic at the Department of Medicine of the Korle-Bu Teaching Hospital and University College Hospital, Ibadan, Nigeria. Patients with Type 2 DM aged 40 years and older were recruited by using systematic random sampling method. The World Health Organization Quality of Life-BREF, diabetes empowerment scale, and DM knowledge scale were used to assess QoL, patient empowerment, and knowledge of DM, respectively. The predictors of QoL were determined using multiple linear regression analyses. RESULTS: A total of 198 patients in Ghana and 203 patients in Nigeria completed the survey, with female-to-male ratio being 3:1 and 2:1, respectively. The overall QoL in both countries was relatively low: 56.19 ± 8.23 in Ghana and 64.34 ± 7.34 in Nigeria. In Ghana, significant correlates of higher scores on the QoL scale were medication adherence (P = 0.02) and employment status (P = 0.02). Among patients in Nigeria, employment status (P = 0.02) and DM empowerment (0.03) were significant predictors of QoL in patients with DM. CONCLUSION: Our study revealed an association between a number of psychosocial factors and QoL among patients with DM in Ghana and Nigeria.

Antibody levels against GLURP R2, MSP1 block 2 hybrid and AS202.11 and the risk of malaria in children living in hyperendemic (Burkina Faso) and hypo-endemic (Ghana) areas.

BACKGROUND: Differences in parasite transmission intensity influence the process of acquisition of host immunity to Plasmodium falciparum malaria and ultimately, the rate of malaria related morbidity and mortality. Potential vaccines being designed to complement current intervention efforts therefore need to be evaluated against different malaria endemicity backgrounds. METHODS: The associations between antibody responses to the chimeric merozoite surface protein 1 block 2 hybrid (MSP1 hybrid), glutamate-rich protein region 2 (GLURP R2) and the peptide AS202.11, and the risk of malaria were assessed in children living in malaria hyperendemic (Burkina Faso, n = 354) and hypo-endemic (Ghana, n = 209) areas. Using the same reagent lots and standardized protocols for both study sites, immunoglobulin (Ig) M, IgG and IgG sub-class levels to each antigen were measured by ELISA in plasma from the children (aged 6-72 months). Associations between antibody levels and risk of malaria were assessed using Cox regression models adjusting for covariates. RESULTS: There was a significant association between GLURP R2 IgG3 and reduced risk of malaria after adjusting age of children in both the Burkinabe (hazard ratio 0.82; 95 % CI 0.74-0.91, p < 0.0001) and the Ghanaian (HR 0.48; 95 % CI 0.25-0.91, p = 0.02) cohorts. MSP1 hybrid IgM was associated (HR 0.85; 95 % CI 0.73-0.98, p = 0.02) with reduced risk of malaria in Burkina Faso cohort while IgG against AS202.11 in the Ghanaian children was associated with increased risk of malaria (HR 1.29; 95 % CI 1.01-1.65, p = 0.04). CONCLUSION: These findings support further development of GLURP R2 and MSP1 block 2 hybrid, perhaps as a fusion vaccine antigen targeting malaria blood stage that can be deployed in areas of varying transmission intensity.

Contraceptive use among HIV-infected women and men receiving antiretroviral therapy in Lusaka, Zambia: a cross-sectional survey.

BACKGROUND: Family planning (FP) is an essential health service and an important part of comprehensive HIV care. However, there is limited information about the contraceptive needs of people living with HIV in sub-Saharan Africa, which in turn has hampered efforts to expand and integrate FP services into existing HIV programs. METHODS: We performed a cross-sectional survey to determine FP prevalence and predictors among HIV-positive women and men attending 18 public antiretroviral therapy (ART) clinics in Lusaka, Zambia. Trained peer counselors administered the 10-question survey to those seeking care for five days at each of the target sites. RESULTS: From February to April 2014, we surveyed 7,046 HIV-infected patients receiving routine HIV services. Use of modern contraception was reported by 69 % of female ART patients and 79 % of male ART patients. However, highly effective contraceptive use and dual method use were low among women (38 and 25 %, respectively) and men (19 and 14 %, respectively). HIV disclosure status (adjusted odds ratio (AOR) = 4.91, 95 % confidence interval (CI) = 3.32-7.24 for women, AOR = 3.58, 95 % CI = 2.39-5.38 for men) and sexual activity in the last 6 months (AOR = 5.80, 95 % CI = 4.51-7.47 for women, AOR = 6.24, 95 % CI = 3.51-11.08 for men) were associated with modern contraceptive use in multivariable regression. Most respondents said they would access FP services if made available within ART clinic. CONCLUSIONS: While FP-ART integration may be a promising strategy for increasing FP service uptake, such services must focus on assessing sexual activity and advocating for dual method use to increase effective contraceptive use and prevent unintended pregnancies.