Search

Background: There is a paucity of information on the contemporary burden, disease patterns, and immunological profile of people living with HIV who are co-infected with C. cayetanensis in the post-antiretroviral therapy era. Methods: For this cross-sectional study, stool samples of 640 HIV-positive and 83 HIV-negative individuals in Ghana were tested for C. cayetanensis. Additionally, sociodemographic parameters, clinical symptoms, medical drug intake, and immunological parameters were assessed. Results: The prevalence of C. cayetanensis was 8.75% (n = 56) in HIV-positive and 1.20% (n = 1) in HIV-negative participants (p = 0.015). Within the group of HIV-positive participants, the prevalence reached 13.6% in patients with CD4+ T cell counts below 200 cells/µl. Frequencies of the clinical manifestations of weight loss and diarrheal disease were significantly higher in patients with C. cayetanensis compared to those without co-infection (36.36% vs. 22.59%, p = 0.034 and 20.00% vs. 4.90%, p < 0.001, respectively). The expression of markers of immune activation and exhaustion of T lymphocyte sub-populations was significantly elevated in patients colonized with C. cayetanensis. Conclusions: In the modern post-combined antiretroviral therapy (cART) era, the acquisition of C. cayetanensis among PLWH in Ghana is driven largely by the immunosuppression profile characterized by high expression of markers of immune activation and immune exhaustion.

Both

BackgroundWorld Health Organizations aims to eliminate mother to child transmission of HIV by 2030. Timely HIV infant diagnostics are required to save the lives of HIV-infected babies which fits into Sustainable development goal 3 (Good health and wellbeing). This study reviews early infant diagnosis (EID) practices at Komfo Anokye Teaching Hospital from January 2020 to August 2021 to assess how this aligns with national policy and its impact on infected infants.MethodsEarly Infant diagnosis tests done on KATH samples were extracted focusing on age, gender, dates sample was drawn/ PCR test was done, and results of tests. Dates were converted to days since birth. Descriptive and inferential statistics were used with statistical significance at p< 0.05 ResultsA total of 400 infants had samples within study period. Test results were available for 98% (392). Data on gender was available for 37% (148) only. Positive results were 8.9% (35/392). By the time infants were sampled for storage, 24.5% (96/392) were within 6 weeks and 8.7% (34/392) were 9 months. The rest, 66.8% (262/392) deviated from protocol. By the time PCR test was done on stored samples, 5.6% (22/392) were within 6 weeks and 3.1% (12/392) were 9 months. The rest, 91.3% (358/392) deviated from protocol. Positive PCR results for deviated protocol was 8.9% (32/358)The median duration from birth to getting samples taken for positive EID case was 97 days compared to 52 days for negative results, p< 0.002. The median duration from birth to getting test results for positive EID case was 186 days compared to 88 days for negative results, p< 0.0002. ConclusionProtocol deviations from EMTCT policy due to delay in reporting contributes to positive EID results. Delay in testing affects start in treatment and negatively impacts neurodevelopment. Positive EID should be fully audited to identify risks.

BackgroundDiagnostic testing for the current SARS-CoV-2 infections involves the collection and testing of invasive pharyngeal specimens by qualified Health workers. Though fully clad in personal protective equipment, the concern is that sampling in close proximity to the patient poses as a major health hazard. The present study sought to verify if saliva or faeces could become a possible surrogate for pharyngeal samples for SARS-CoV 2 testing in suspected Ghanaian COVID-19 patients.ObjectivesTo ascertain if there is SARS-CoV 2 viral shedding in the saliva and faecal samples of Ghanaian COVID-19 patients, their sensitivity and specificity as compared to pharyngeal samples.MethodFifty (50) recruited COVID-19 patients who have been confirmed via RT-PCR using their nasopharyngeal/oropharyngeal samples and twenty (20) SARS-CoV 2 negative suspected patients each provided some faecal and saliva sample for RT-PCR analysis for SARS-CoV 2.ResultsForty-three (43) out of the fifty (50) COVID-19 patients recruited representing 86% tested positive for SARS-CoV 2 via their saliva sample whiles all their faecal samples tested positive for SARS-CoV 2 representing 100%. The sensitivity of saliva samples was 86% whiles the specificity was 100% but the sensitivity and specificity of the faecal samples were all 100%.ConclusionThere is indeed viral shedding of SARS-CoV 2 in the saliva and faeces of Ghanaian COVID-19 patients just like their counterparts in other parts of the world. Saliva and faeces could possibly become an alternative sample to the current in place of the invasive pharyngeal samples for SARS-CoV 2 testing in resource limited settings. Further research to explore this possibility at different testing sites with larger sample size is recommended.

Background: Recent studies demonstrated higher prevalence rates of Tropheryma whipplei (T. whipplei) in HIV positive than in HIV negative subjects. However, associations with the immune status in HIV positive participants were conflicting. Methods: For this cross-sectional study, stool samples of 906 HIV positive and 98 HIV negative individuals in Ghana were tested for T. whipplei. Additionally, sociodemographic parameters, clinical symptoms, medical drug intake, and laboratory parameters were assessed. Results: The prevalence of T. whipplei was 5.85% in HIV positive and 2.04% in HIV negative participants. Within the group of HIV positive participants, the prevalence reached 7.18% in patients without co-trimoxazole prophylaxis, 10.26% in subjects with ART intake, and 12.31% in obese participants. Frequencies of clinical symptoms were not found to be higher in HIV positive T. whipplei carriers compared to T. whipplei negative participants. Markers of immune activation were lower in patients colonized with T. whipplei. Multivariate regression models demonstrated an independent relationship of a high CD4+ T cell count, a low HIV-1 viral load, and an obese body weight with the presence of T. whipplei. Conclusions: Among HIV positive individuals, T. whipplei colonization was associated with a better immune status but not with clinical consequences. Our data suggest that the withdrawal of co-trimoxazole chemoprophylaxis among people living with HIV on stable cART regimen may inadvertently increase the propensity towards colonization with T. whipplei.

Objectives The current WHO weight-based dosing recommendations for efavirenz result in a wide variability of drug exposure in children. Our objectives are to characterize the effects of rifampicin- and isoniazid-containing anti-TB therapy and CYP2B6 activity on efavirenz concentrations in children, using non-linear mixed-effects modelling. Methods This is a pharmacokinetic (PK) substudy of a prospective study that examined the interactions between anti-TB therapy and efavirenz in HIV-infected children with and without TB. PK samples were obtained 4 weeks after starting efavirenz (PK1) and repeated 4 weeks after completing TB therapy (PK2) in TB/HIV coinfected patients. Drug concentrations were measured using LC-MS/MS. Composite CYP2B6 516/983/15582 genotype was determined. Population PK modelling was performed in Monolix. Simulations were performed to obtain the predicted mid-dose concentrations (C12). Results One hundred and five HIV-infected Ghanaian children (46 with TB/HIV) were included. The median age and weight were 7 years and 19 kg. The efavirenz concentrations over time were adequately described using a one-compartment model. Weight, composite CYP2B6 genotype and PK visit had a significant influence on the PK parameters, while TB therapy had no significant effect. Simulations showed adequate C12 for intermediate composite CYP2B6 metabolizers only. Conclusions Our model showed that rifampicin- and isoniazid-containing anti-TB therapy does not influence efavirenz PK parameters. On the other hand, it describes the effect of efavirenz autoinduction after completing TB treatment. In addition, dosing efavirenz in children based only on weight results in a large variability in drug exposure. We propose dose adjustments for slow and extensive composite CYP2B6 metabolizers.

Background The services of most clinical laboratories in Africa regarding the diagnosis of Trichomonas vaginalis are largely dependent on the urine direct wet-mount method. However, the exclusive use of urine-based detection may not be appropriate. The culture method is considered the “gold standard” for the diagnosis of T. vaginalis. However, this method has a relatively longer turn-around time and is limited by non-viable organisms in the specimen. This study assessed the prevalence of T. vaginalis and its associated risk factors and evaluated its diagnosis using urine and vaginal samples from symptomatic female out-patients by culture, direct wet-mount, and ELISA method respectively. Methods This cross-sectional study was conducted at the Obstetrics and Gynaecology department of the Manhyia District hospital (MDH) and Komfo Anokye Teaching Hospital (KATH), Ghana. Ghanaian sexually active female adults between the ages of 18 and 50 years old were recruited for this study. Vaginal (HVS) and urine samples were collected from each participant, and T. vaginalis infection was assessed based on culture, direct wet mount, and ELISA methods. Results The prevalence of T. vaginalis infection based on the ELISA method, HVS culture, and HVS wet mount were 7.2%, 5.0%, and 1.7%, respectively. Urine culture presented with a 0.6% prevalence rate while urine direct wet mount detected no positive case. There was no statistically significant association between demographic and clinical characteristics and T. vaginalis infection, except for subjects presenting with abdominal pain [OR = 5.42, 95% CI (1.35–21.73), p = 0.017]. Using HVS culture as the reference, ELISA performed best compared to the other methods assessed in this study, presenting with the highest sensitivity [88.9%, 95% CI (54.0–99.8)], specificity [97.1%, 95% CI (93.1–98.9)], AUC (93.0%), and accuracy (96.7%). Conclusion The prevalence of T. vaginalis infection is high among women in Ghana. With the exception of abdominal pain, there is no significant association between demographic and clinical characteristics and T. vaginalis infection. In the event where the culture method is unavailable or when rapid diagnosis is required, antigenic detection using ELISA is the most accurate for the diagnosis of T. vaginalis infection in women compared to urine wet-mount/culture and the HVS wet-mount method.

BACKGROUND: Anti-TB drugs dosing based on weight alone may contribute to suboptimal drug concentrations and poor treatment outcomes in malnourished children. We examined the effect of malnutrition on the pharmacokinetics (PK) of first-line anti-TB drugs in children.METHODS: Drug concentrations were measured in Ghanaian children during the intensive phase of TB treatment. Weight-for-age (WFA), height-for-age (HFA), weight-for-height (WFH) and body mass index-for-age (BFA) were calculated and children with Z-scores < -2 SD (standard deviations) were considered as having malnutrition. PK differences of anti-TB drugs were compared by nutritional status.RESULTS: Of 100 participants, 24/48 (50.0%) of those younger than 5 years had wasting, 58/86 (67.4%) were underweight, and 56/99 (56.6%) had stunting; 22/51 (43.1%) children aged ≥5 years had low BFA. Children with stunting were more likely than controls to have lower mean peak concentration (Cmax) and area under the curve (AUC0–8h) of rifampin (RIF) and pyrazinamide (PZA), as well as a higher frequency of Cmax below the normal range. Wasting and underweight were associated with lower mean ethambutol (EMB) Cmax and AUC0–8h.CONCLUSIONS: The current WHO-recommended dosages were associated with lower plasma exposure of RIF, PZA and EMB in children with stunting, wasting and underweight. Anti-TB drugs dosing models for children may need to include height.

Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor that is used in the treatment of human immunodeficiency virus (HIV) infection in children younger than 3 years old. Identifying genetic predictors of NVP pharmacokinetics (PK) in young children is important because inter-individual variability in NVP concentrations contributes to variable treatment response and the information may be used to individualize dosing decisions. We examined the relationship between genetic variations in relevant drug disposition genes and NVP PK parameters in Ghanaian children living with HIV eligible to initiate NVP-based antiretroviral therapy. Participants received NVP plus zidovudine and lamivudine or abacavir and lamivudine twice daily, and those with tuberculosis (TB) coinfection received concurrent anti-TB therapy with NVP. Pharmacokinetic sampling was performed after at least 4 weeks of antiretroviral therapy. Nevirapine minimum concentration (Cmin), area under the concentration-time curve from time 0 to 12 h (AUC0–12h), and apparent clearance (CL/F) were calculated using non-compartmental analysis using Phoenix v8.0 software. Genotyping for CYP2B6, CYP2A6, CYP3A5, ABCB1, NR1I2, and NR1I3 single nucleotide polymorphism (SNPs) was performed by TaqMan® allelic discrimination method. The median (range) NVP dose received was 10 (7–14) mg/kg. Of the 53 participants, the median (range) Cmin was 3.3 (0.0–14.0) mg/L and AUC0–12h was 56.0 (16.7–202.6) mg.hr/L. Using step-wise regression, CYP2B6 rs3745274 and NR1I2 rs6785049 SNPs were independent as well as joint predictors of NVP AUC0–12h, Cmin, and CL/F. We concluded that genotyping for CYP2B6 rs3745274, and the NR1I2 rs6785049 G > A SNP (which encodes the transcriptional factor, pregnane X receptor), could improve prediction of NVP PK for individualized therapy.

In the post-polio eradication era, increasing attention is given to non-polio enteroviruses. Most of the data about enteroviruses in sub-Saharan Africa are related to acute flaccid paralysis surveillance and target the pediatric population. This study aimed to investigate the presence of enterovirus in PLHIV (people living with HIV) and HIV-negative individuals in Ghana. Stool samples from HIV-positive individuals (n = 250) and healthy blood donors (n = 102) attending the Komfo Anokye Teaching Hospital in Kumasi, Ghana, were screened by real-time PCR for enterovirus. Molecular typing of the VP1 region was performed. Enterovirus-positive samples were tested for norovirus, adenovirus, rotavirus, sapovirus, and cosaviruses. Twenty-six out of 250 HIV-positive subjects (10.4%) and 14 out of 102 HIV-negative individuals (13.7%) were detected enterovirus-positive, not showing a significant different infection rate between the two groups. HIV-negative individuals were infected with Enterovirus C strains only. HIV-positive participants were detected positive for species Enterovirus A, Enterovirus B, and Enterovirus C. Co-infections with other viral enteric pathogens were almost exclusively detected among HIV-positive participants. Overall, the present study provides the first data about enteroviruses within HIV-positive and HIV-negative adults living in Ghana.

BACKGROUND The World Health Organization recommended increased dosages of the first-line antituberculosis (anti-TB) drugs for children in 2010. We examined the frequency of and factors associated with low plasma maximum concentration (Cmax) of each drug in children treated with the revised dosages. METHODS Children on anti-TB therapy for at least 4 weeks underwent pharmacokinetic testing. Plasma Cmax below the lower limit of proposed reference range was considered low. Bivariate and multivariate analyses were used to examine the factors associated with low Cmax of each drug. RESULTS Of the 100 children, 58% were male, 50% HIV-infected and 49% younger than 5 years old. The median (interquartile range) Cmax was 5.9 (4.5-7.7) µg/mL for isoniazid, 6.5 (4.9-8.8) µg/mL for rifampin, 26.0 (21.2-33.4) µg/mL for pyrazinamide and 1.7 (0.9-2.7) µg/mL for ethambutol. There was a strong correlation between Cmax and AUC0-8h for all drugs. Low Cmax occurred in 9/100 (9.0%), 61/100 (61.0%), 17/97 (17.5%) and 60/97 (61.9%) for isoniazid, rifampin, pyrazinamide and ethambutol, respectively. In addition, 75/97 (77.3%) children had pyrazinamide Cmax < 35 µg/mL. Factors associated with low Cmax were NAT2 metabolizer phenotype status for isoniazid; height, dosage and HIV coinfection status for rifampin; height for pyrazinamide; and age, dosage and HIV coinfection status for ethambutol. CONCLUSIONS The high frequency of low rifampin and ethambutol Cmax in our study is consistent with emerging pharmacokinetic data in children treated according to the new WHO recommendations. Higher dosages than currently recommended especially for rifampin may be necessary in children.

Background Type II diabetes mellitus (T2DM) is complicated by multiple cardio-metabolic risk factors. Controlling these factors requires lifestyle modifications alongside utilisation of anti-diabetic medications. Different glucose lowering [(biguanides (BIGs), sulfonylureas (SUAs), thiazolidinediones (TNZ)], lipid lowering (statins), and anti-hypertensive medicines [angiotensin converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs) and central acting drugs (CADs)] have been approved for controlling hyperglycaemia, dyslipidaemia and hypertension respectively. Here, we examined factors that characterise T2DM and explored the response to medication therapy among T2DM patients. Methods This prospective cohort study recruited 241 T2DM patients reporting at a clinic in Ghana, from January through to August, 2016. Each patient’s demographic, medications and anthropometric data was obtained while information on medication adherence was captured using Morisky adherence scale-8 (MMAS-8). Fasting blood samples were collected for biochemical analysis. Results The mean age of participants was 57.82 years for baseline and six-month follow-up. Physical activity differed at baseline and follow up (p 0.05). Many participants using either ACEI or ARB were able to control their blood pressures. Among dyslipidaemia patients under statin treatment, there was an improved lipid profile at follow-up. Conclusions Statin medications are effective for reducing dyslipidaemia in T2DM patients. However, control of modifiable risk factors, particularly blood glucose and to a lesser degree blood pressure is suboptimal. Addressing these will require concomitant interventions including education on medication adherence and correct dietary plans, lifestyle modifications and physical activity. Electronic supplementary material The online version of this article (doi:10.1186/s40169-017-0162-5) contains supplementary material, which is available to authorized users.

Nevirapine-based antiretroviral therapy (ART) is one of the limited options in HIV-infected children younger than 3 years old (young children) with tuberculosis (TB) coinfection. To date, there are insufficient data to recommend nevirapine-based therapy during first-line antituberculosis (anti-TB) therapy in young children. We compared nevirapine pharmacokinetics (PK) in HIV-infected young children with and without TB coinfection. In the coinfected group, nevirapine PK was evaluated while on anti-TB therapy and after completing an anti-TB therapy regimen. Of 53 participants, 23 (43%) had TB-HIV coinfection. While the mean difference in nevirapine PK parameters between the two groups was not significant (P > 0.05), 14/23 (61%) of the children with TB-HIV coinfection and 9/30 (30%) with HIV infection had a nevirapine minimum concentration (C(min)) below the proposed target of 3.0 mg/liter (P = 0.03). In multivariate analysis, anti-TB therapy and the CYP2B6 516G>T genotype were joint predictors of nevirapine PK parameters. Differences in nevirapine PK parameters between the two groups were significant in children with CYP2B6 516GG but not the GT or TT genotype. Among 14 TB-HIV-coinfected participants with paired data, the geometric mean C(min) and area under the drug concentration-time curve from time zero to 12 h (AUC(0–12)) were about 34% lower when patients were taking anti-TB therapy, while the nevirapine apparent oral clearance (CL/F) was about 45% higher. While the induction effect of anti-TB therapy on nevirapine PK in our study was modest, the CYP2B6 genotype-dependent variability in the TB drug regimen effect would complicate any dose adjustment strategy in young children with TB-HIV coinfection. Alternate ART regimens that are more compatible with TB treatment in this age group are needed. (This study has been registered at ClinicalTrials.gov under identifier NCT01699633.)

We compared efavirenz pharmacokinetic (PK) parameters in children with tuberculosis (TB)/human immunodeficiency virus (HIV) coinfection on and off first-line antituberculosis therapy to that in HIV-infected children. Children 3 to 14 years old with HIV infection, with and without TB, were treated with standard efavirenz-based antiretroviral therapy without any efavirenz dose adjustments., We compared efavirenz pharmacokinetic (PK) parameters in children with tuberculosis (TB)/human immunodeficiency virus (HIV) coinfection on and off first-line antituberculosis therapy to that in HIV-infected children. Children 3 to 14 years old with HIV infection, with and without TB, were treated with standard efavirenz-based antiretroviral therapy without any efavirenz dose adjustments. The new World Health Organization-recommended antituberculosis drug dosages were used in the coinfected participants. Steady-state efavirenz concentrations after 4 weeks of antiretroviral therapy were measured using validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) assays. Pharmacokinetic parameters were calculated using noncompartmental analysis. Between groups, PK parameters were compared by Wilcoxon rank-sum test and within group by signed-rank test. Of the 105 participants, 43 (41.0%) had TB coinfection. Children with TB/HIV coinfection compared to those with HIV infection were younger, had lower median weight-for-age Z score, and received a higher median efavirenz weight-adjusted dose. Geometric mean (GM) efavirenz peak concentration (Cmax), concentration at 12 h (C12h), Cmin, and total area under the curve from time 0 to 24 h (AUC0–24h) values were similar in children with HIV infection and those with TB/HIV coinfection during anti-TB therapy. Geometric mean efavirenz C12h, Cmin, and AUC0–24h values were lower in TB/HIV-coinfected patients off anti-TB therapy than in the children with HIV infection or TB/HIV coinfection on anti-TB therapy. Efavirenz clearance was lower and AUC0–24h was higher on than in patients off anti-TB therapy. Reduced efavirenz clearance by first-line anti-TB therapy at the population level led to similar PK parameters in HIV-infected children with and without TB coinfection. Our findings do not support modification of efavirenz weight-band dosing guidelines based on TB coinfection status in children. (The study was registered with ClinicalTrials.gov under registration number NCT01704144.)

BackgroundThe study assessed the hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection paradigm among the human immunodeficiency virus (HIV) infected patients attending a tertiary hospital in Ghana. Also, the immunological and virological characterisation of these viruses, prior to antiretroviral therapy (ART) initiation was investigated.MethodA total of 400 HIV infected (HIV type-1) treatment naïve subjects ≥18 years were enrolled and tested for HBsAg and anti-HCV. Hepatitis B virus serological profile was performed on samples that were HBV positive. CD4+ T-cell count and HIV-1 RNA viral loads were determined using BD FacsCalibur analyzer (USA) and COBAS AmpliPrep/COBAS TaqMan Analyzer (USA) respectively.ResultsThe overall prevalence of HBV/HCV co-infection among the HIV-1 patients was 18.0%. The prevalence of HIV-HBV and HIV-HCV co-infections were 12.5% and 5.5% respectively. The prevalence of active viral hepatitis (HBeAg-positive) among HIV-HBV co-infected patients was 40%. None of the patients had anti-HBc IgM. HIV-HBV co-infection was associated with lower CD4+ T-cell count as well as higher HIV-1 viral load compared to both HIV mono- infection and HIV-HCV co- infection (pConclusionThe present study highlights the predominance of HBV exposure among the HIV infected patients in Ghana. HBV coinfection was associated with severe immunosuppression and higher HIV-1 viral load.

Inflammation is the immune response of the body to infection and injury. Inflammation aims at eliminating the pathogen or causative agent, removing necrotic cells and tissues and initiating repair process. IL-6. TNF-α and CRP are biomarkers of inflammation. This study sought to determine the pro-inflammatory markers among HIV patients on HAART and HAART naïve patients. This was a hospital-based, case control study conducted among 150 participants. HIV patients’ on HAART (n = 50) and HAART naïve HIV (n = 50) patients and the control group (n = 50) was HIV Seronegative individuals. Venous blood was drawn from each of the participant. Serial dilutions of standards of TNF-α, IL-6 and CRP were made and mixed with 10 μL of patients’ blood. Absorbance was read at 450 nm within 15 min with Mindray MR-96A reader. Among the study population, IL-6 levels was higher in HAART naïve HIV patients 17.66(13.00 - 24.10) ng/L, and these same group also recorded the highest CRP and TNF-α levels of 1453(328.8 – 2510) µg/L and 318.3(123.0 - 497.9) ng/L respectively. The present study revealed elevated levels of pro-inflammatory cytokines (IL-6, CRP and TNF-α) in seropositive HIV groups compared to seronegative group.&nbsp

Isoniazid and rifampin are essential components of first-line antituberculosis (anti-TB) therapy. Understanding the relationship between genetic factors and the pharmacokinetics of these drugs could be useful in optimizing treatment outcomes, but this is understudied in children. We investigated the relationship between N-acetyltransferase type 2 ( NAT2 ) genotypes and isoniazid pharmacokinetics, as well as that between the solute carrier organic anion transporter family member 1B1 (encoded by SLCO1B1 ) and carboxylesterase 2 ( CES2 ) single nucleotide polymorphisms (SNPs) and rifampin pharmacokinetics in Ghanaian children. Blood samples were collected at times 0, 1, 2, 4, and 8 h postdose in children with tuberculosis on standard first-line therapy for at least 4 weeks. Isoniazid and rifampin concentrations were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and pharmacokinetic parameters were calculated using noncompartmental analysis. Genotyping of NAT2 , SLCO1B1 , and CES2 SNPs were performed using validated TaqMan genotyping assays. The Kruskal-Wallis test was used to compare pharmacokinetic parameters among the three genotypic groups and was followed by the Wilcoxon rank sum test for pairwise group comparisons. Genotype status inferred by the NAT2 4-SNP and 7-SNP genotyping panels identified children with a slow acetylator phenotype but not the rapid genotype. For rifampin, only the rare SLCO1B1*1b homozygous variant was associated with rifampin pharmacokinetics. Our findings suggest that NAT2 and SCLCO1B1*1b genotyping may have minimal clinical utility in dosing decisions at the population level in Ghanaian children, but it could be useful at the individual level or in populations that have a high frequency of implicated genotypes. Further studies in other populations are warranted.

Optimal doses for antituberculosis (anti-TB) drugs in children have yet to be established. In 2010, the World Health Organization (WHO) recommended revised dosages of the first-line anti-TB drugs for children. Pharmacokinetic (PK) studies that investigated the adequacy of the WHO revised dosages to date have yielded conflicting results. We performed population PK modeling using data from one of these studies to identify optimal dosage ranges. Ghanaian children with tuberculosis on recommended therapy with rifampin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol (EMB) for at least 4 weeks had blood samples collected predose and at 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid chromatography-mass spectrometry methods. Nonlinear mixed-effects models were applied to describe the population PK of those drugs using MonolixSuite2016R1 (Lixoft, France). Bayesian estimation was performed, the correlation coefficient, bias, and precision between the observed and predicted areas under the concentration-time curve (AUCs) were calculated, and Bland-Altman plots were analyzed. The population PK of RIF and PZA was described by a one-compartment model and that for INH and EMB by a two-compartment model. Plasma maximum concentration (C(max)) and AUC targets were based on published results for children from India. The lowest target values for pediatric TB patients were attainable at the WHO-recommended dosage schedule for RIF and INH, except for N-acetyltransferase 2 non-slow acetylators (rapid and intermediate acetylators) in the lower-weight bands. However, higher published adult targets were not attainable for RIF and INH. The targets were not achieved for PZA and EMB. (This study has been registered at ClinicalTrials.gov under identifier NCT01687504.)

Isoniazid and rifampin are essential components of first-line antituberculosis (anti-TB) therapy. Understanding the relationship between genetic factors and the pharmacokinetics of these drugs could be useful in optimizing treatment outcomes, but this is understudied in children. We investigated the relationship between N-acetyltransferase type 2 (NAT2) genotypes and isoniazid pharmacokinetics, as well as that between the solute carrier organic anion transporter family member 1B1 (encoded by SLCO1B1) and carboxylesterase 2 (CES2) single nucleotide polymorphisms (SNPs) and rifampin pharmacokinetics in Ghanaian children. Blood samples were collected at times 0, 1, 2, 4, and 8 h postdose in children with tuberculosis on standard first-line therapy for at least 4 weeks. Isoniazid and rifampin concentrations were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and pharmacokinetic parameters were calculated using noncompartmental analysis. Genotyping of NAT2, SLCO1B1, and CES2 SNPs were performed using validated TaqMan genotyping assays. The Kruskal-Wallis test was used to compare pharmacokinetic parameters among the three genotypic groups and was followed by the Wilcoxon rank sum test for pairwise group comparisons. Genotype status inferred by the NAT2 4-SNP and 7-SNP genotyping panels identified children with a slow acetylator phenotype but not the rapid genotype. For rifampin, only the rare SLCO1B1*1b homozygous variant was associated with rifampin pharmacokinetics. Our findings suggest that NAT2 and SCLCO1B1*1b genotyping may have minimal clinical utility in dosing decisions at the population level in Ghanaian children, but it could be useful at the individual level or in populations that have a high frequency of implicated genotypes. Further studies in other populations are warranted.

Background Helicobacter pylori coinfection in human immunodeficiency virus (HIV) patients has been associated with higher CD4+ cell counts and lower HIV-1 viral loads, with the underlying mechanisms being unknown. The objective of this study was to investigate the impact of H. pylori infection on markers of T-cell activation in HIV-positive and HIV-negative individuals. Methods In a cross-sectional, observational study, HIV patients (n = 457) and HIV-negative blood donors (n = 79) presenting to an HIV clinic in Ghana were enrolled. Data on clinical and sociodemographic parameters, CD4+/CD8+ T-cell counts, and HIV-1 viral load were recorded. Helicobacter pylori status was tested using a stool antigen test. Cell surface and intracellular markers related to T-cell immune activation and turnover were quantified by flow cytometry and compared according to HIV and H. pylori status. Results Helicobacter pylori infection was associated with decreased markers of CD4+ T-cell activation (HLA-DR+CD38+CD4+; 22.55% vs 32.70%; P = .002), cell proliferation (Ki67; 15.10% vs 26.80%; P = .016), and immune exhaustion (PD-1; 32.45% vs 40.00%; P = .005) in 243 antiretroviral therapy (ART)-naive patients, but not in 214 patients on ART. In HIV-negative individuals, H. pylori infection was associated with decreased frequencies of activated CD4+ and CD8+ T cells (6.31% vs 10.40%; P = .014 and 18.70% vs 34.85%, P = .006, respectively). Conclusions Our findings suggest that H. pylori coinfection effectuates a systemic immune modulatory effect with decreased T-cell activation in HIV-positive, ART-naive patients but also in HIV-negative individuals. This finding might, in part, explain the observed association of H. pylori infection with favorable parameters of HIV disease progression. Clinical trials registration Clinicaltrials.gov NCT01897909.

Although human immunodeficiency virus (HIV) coinfection is the most important risk factor for a poor antituberculosis (anti-TB) treatment response, its effect on the pharmacokinetics of the first-line drugs in children is understudied. This study examined the pharmacokinetics of the four first-line anti-TB drugs in children with TB with and without HIV coinfection. Ghanaian children with TB on isoniazid, rifampin, pyrazinamide, and ethambutol for at least 4 weeks had blood samples collected predose and at 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid chromatography-mass spectrometry methods and pharmacokinetic parameters calculated using noncompartmental analysis. The area under the concentration-time curve from 0 to 8 h (AUC 0–8 ), maximum concentration ( C max ), and apparent oral clearance divided by bioavailability (CL/F) for each drug were compared between children with and without HIV coinfection. Of 113 participants, 59 (52.2%) had HIV coinfection. The baseline characteristics were similar except that the coinfected patients were more likely to have lower weight-for-age and height-for-age Z scores ( P < 0.05). Rifampin, pyrazinamide, and ethambutol median body weight-normalized CL/F values were significantly higher, whereas the plasma AUC 0–8 values were lower, in the coinfected children than in those with TB alone. In the multivariate analysis, drug dose and HIV coinfection jointly influenced the apparent oral clearance and AUC 0–8 for rifampin, pyrazinamide, and ethambutol. Isoniazid pharmacokinetics were not different by HIV coinfection status. HIV coinfection was associated with lower plasma exposure of three of the four first-line anti-TB drugs in children. Whether TB/HIV-coinfected children need higher dosages of rifampin, pyrazinamide, and ethambutol requires further investigation. (This study has been registered at ClinicalTrials.gov under identifier NCT01687504.)

Background Worldwide, there is a high co-endemicity of HIV and H. pylori infection and there is growing evidence that H. pylori co-infection is associated with parameters of HIV disease progression. The objective of this study was to investigate the prevalence of H. pylori infection, and the association with clinical, immunological and virological parameters in a large cohort of HIV-infected individuals and uninfected controls in a West African country. Methods HIV-patients (n = 1,095) and HIV-negative individuals (n = 107) were recruited at a university hospital in Ghana. H. pylori status was determined using stool antigen testing. HIV-related, clinical and socio-demographic parameters were recorded and analyzed according to H. pylori status. Results The prevalence of H. pylori infection was significantly lower in HIV-positive compared to HIV-negative individuals (51.5 vs. 88%, p

Background. Pharmacokinetic data on the first-line antituberculosis drugs using the World Health Organization (WHO) revised dosages for children are limited. We investigated the pharmacokinetics of these drugs in children who were mostly treated with revised dosages. Methods. Children with tuberculosis on first-line therapy for at least 4 weeks had blood samples collected at predose, 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid chromatography mass spectrometry methods, and pharmacokinetic parameters were calculated using noncompartmental analysis. Factors associated with plasma peak concentration (Cmax) and the area under the time–concentration curve 0–8 hours (AUC0–8h) of each drug was examined using univariate and multivariate analysis. Results. Of the 62 children, 32 (51.6%) were male, 29 (46.8%) wereyounger than 5 years old, and 28 (45.2%) had human immunodeficiency virus (HIV) coinfection. Three patients had undetectable pyrazinamide and ethambutol concentrations. The median (interquartile range) AUC0–8h for isoniazid was 17.7 (10.2–23.4) µg·h mL –1 , rifampin was 26.0 (15.3–36.1) µg·h mL –1 , pyrazinamide was 144.6 (111.5–201.2) µg·h mL –1 , and ethambutol was 6.7 (3.8–10.4) µg·h mL –1 . Of the children who received recommended weight-band dosages, 44/51 (86.3%), 46/56 (82.1%), 27/56 (48.2%), and 21/51 (41.2%) achieved target Cmax for isoniazid, pyrazinamide, ethambutol, and rifampin, respectively. In multivariate analysis, age, sex, HIV coinfection status, and drug dosage in milligrams per kilogram were associated with the drugs’ plasma drug Cmax or AUC0–8h. Conclusions. The revised dosages appeared to be adequate for isoniazid and pyrazinamide, but not for rifampin or ethambutol in this population. Higher dosages of rifampin and ethambutol than currently recommended may be required in most children.

Paired Ghanaian plasma and cord blood from pregnant women, alongside plasma samples from children aged 1 day to 70 months, were tested for GBV-C, HIV-1 RNA loads and anti-E2. Frequency of GBV-C vertical transmission in West Africa is significantly lower than in Europe, the USA or East Asia where genotype 2 or 3 is prevalent. While horizontal transmission appears predominant in West Africa, the lower viral load of African genotype 1 might explain limited vertical transmission.

Antibodies to influenza virus and human immunodeficiency virus are detectable in B cells during the early stages of the immune response, prior to their occurrence in plasma. To investigate similar phenomena in a model of immunization against hepatitis B virus (HBV) infection, medical students in Ghana were screened for HBV markers, HBV surface (HBs) antigen (HBsAg), and HBV core antibodies (anti-HBc). Consenting volunteers, 24 of whom were seronegative (susceptible) and 2 of whom were positive for anti-HBc (prior infection), were vaccinated on day 0, day 40, and 6 months. Two sets of 10 blood samples, sequentially collected at intervals of 2 days following each immunization on days 0 and 40, were processed into B-cell lysates and plasma. Solid-phase HBsAg coated on microtiter plates for enzyme immunoassay or nitrocellulose membranes for dot blot assay was used to detect anti-HBs activity by an indirect antiglobulin assay. A commercially procured sandwich immunoassay was used, along with an enzyme-linked immunosorbent assay and a dot blot assay, for the detection of anti-HBs in B-cell lysates and plasma. Following the first injection of vaccine, a single sample of B-cell lysate collected between 5 and 21 days revealed anti-HBs in 18/21 subjects with no plasma antibodies detectable by sandwich immunoassay. After the booster dose was injected on day 40, a single sample of B-cell lysate collected between 44 and 49 days showed anti-HBs in 16/19 subjects, and this was accompanied by plasma antibodies in 8 subjects. In contrast, between 8 and 13 days, both subjects with prior HBV infection showed anti-HBs in B-cell lysates and plasma. Thus, primary immunization with the HBV vaccine appears to transiently elicit low-affinity anti-HBs in B-cell lysates into plasma.

Background: Investigations on the impact of GB virus C (GBV-C) co-infection on HIV disease progression relied essentially on clinical follow-up but not on virologic parameters. Objectives: To detect and quantify GBV-C RNA in West African populations co-infected or not with HIV-1 and to correlate the RNA load of HIV-1 and GBV-C in co-replicating patients with different clinical conditions. Methods: Three Ghanaian populations (blood donors, pregnant women and HIV-infected patients) were subdivided into six groups according to HIV-1 and clinical status and GBV-C and HIV-1 RNA load was tested by quantitative real time reverse transcriptase-polymerase chain reaction. In one population with HIV-1 disease, CD4+ cell count was also measured. Results: Prevalence of GBV-C markers in HIV-1-infected groups and HIV-1 non-infected pregnant women were significantly higher than in healthy blood donors. Similar levels and distribution of GBV-C RNA load were found in each population irrespective of HIV-1 status except for a lower GBV-C RNA load in AIDS patients. There was a significant shift of HIV-1 load towards lower value when GBV-C RNA was present and a trend towards an inverse correlation between HIV-1 and GBV-C RNA load. A positive correlation between CD4+ cell count and GBV-C RNA load in symptomatic HIV-1-infected patients was observed. Conclusions: The moderate impact of GBV-C on HIV-1 viremia is unlikely to entirely account for a favourable clinical outcome of replicating co-infections.

Plasma samples obtained at delivery from 885 pregnant Ghanaian women were tested for human parvovirus B19 DNA and B19-specific antibodies. Maternal-fetal transmission was evaluated by testing paired maternal plasma and umbilical cord blood samples, as well as newborn whole-blood samples when they were available. The B19 DNA seroprevalence rate in women was 1.8% (94% had genotype 3 strains), and the immunoglobulin G (IgG) seroprevalence rate in women was 81%. Two of 3 cases of primary maternal B19 infection resulted in fetal transmission. Coexistence of B19 DNA and B19-specific IgG (persistence) was detected in 13 women (1.5%), but no transmission of the virus was observed. Contrary to the situation in pregnant women with primary B19 infection and high viral loads, pregnant women with low viral loads and B19-specific IgG do not appear to be vertically infectious.

HIV RNA detection in the newborn is the main diagnostic tool for vertical transmission. Most infections are thought to occur peri- or post-natally, hence preventive antiviral therapy administered days before and during delivery. This study used cord blood for molecular diagnosis, examined viral load and HIV-1 subtypes as determinants of transmission, and compared molecular variability of maternal, cord blood, and post-natal quasispecies. Ninety-seven seropositive mother-cord blood paired plasmas from Ghana were tested for HIV RNA. Viral load was quantified and a subgroup of 45 random women samples was typed and subtyped. HIV-1 from infected pairs was cloned, sequenced, and analyzed phylogenetically. The prevalence of HIV infection in pregnant women was 3.3%. 13/97 cord blood samples (13.5%) contained HIV RNA. No correlation between either viral load at labor (range 10(3)-10(7)) or HIV-1 subtype and in utero transmission was found. In both transmitting and non-transmitting mothers, 56% of HIV-1 strains were CRF02_AG. In three pairs, maternal and cord blood quasispecies were closely related, suggesting late pregnancy or perinatal transmission, while in four pairs, genetic distances suggested transmission earlier during gestation. Maternal viral load and genotype did not correlate with HIV-1 pre-natal transmission. HIV infection during gestation appears relatively frequent.