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Introduction: The Coronavirus disease 2019 (COVID-19) has become a cause of significant morbidity and mortality in the world. There are currently 4 COVID-19 vaccines have been developed for mass vaccination to combat the disease. Some people, however, have expressed safety and efficacy concerns with regards to the vaccines. In Ghana, junior doctors, being frontline doctors, are likely to first encounter patients presenting with COVID-19. They may also have the highest direct exposure to the virus even though their outcomes after infection may be good. The study sought to determine the potential acceptance rate of COVID-19 vaccine among junior doctors, the factors that will influence their acceptance and whether they will recommend the vaccine to their patients. Methods: The study was an ethically approved anonymous cross-sectional survey to determine the willingness to accept the SARS-CoV-2 vaccine among junior doctors in Ghana. The survey was designed using Google forms posted to the various junior doctor’s social media group pages such as WhatsApp and Facebook with the study participants responding to 15 items. Results: Out of a total of 305 participants, females were 155 (50.8%). Of the respondents, 171/305 (56.1%) had cared for Covid-19 patients before, 51/305 (16.7%) had had Covid-19 infection previously and 204/305 (66.9%) will be willing to take the vaccine when available. Females were more likely to take the vaccine and those who were willing to accept the vaccine were more likely to recommend same to their family and others. Conclusion: This study has showed a more than average willingness to accept the COVID-19 vaccine. Female gender, living with the extended family and history of SARS-Cov-2 infection were positively associated with willingness to accept the COVID-19 vaccine. Doctors who were willing to accept the vaccine were also more likely to recommend their patients and family members to also accept the COVID-19 vaccine.

Introduction:A pregnant woman’s knowledge of her human immune deficiency virus (HIV) serostatus and that of her sexual partner and the disclosure of her serostatus to the partner puts her in a better position to make informed choices about her pregnancy, adopt strategies to prevent mother to child transmission (PMTCT) of HIV and reduce sexual transmission of HIV. Some pregnant women however opt out of antenatal HIV testing while others have challenges with partner disclosure. This study sought to assess the pregnant women’s knowledge of their HIV serostatus and that of their partners, and disclosure to partners about their serostatus. Methods:An ethically approved cross-sectional descriptive study was conducted at the antenatal clinic (ANC) of the Kumasi South Hospital, Ghana from the period 8thMarch to 5thApril, 2016. A structured questionnaire was administered to 407 ANC attendants who were randomly selected to participate in the study. Data entry was in Microsoft Excel and analyzed using R Core Team (2014). Results:The study showed that 80.1% (n = 326/407) of the participants knew their HIV serostatus. Of these, 18.1% (n = 59/326) knew prior to the current pregnancy and 81.9% (n = 267/326) were told during the current pregnancy. Among those who knew their HIV serostatus, the majority [83.1%; (n = 271/326)] had disclosed to their partners. Most of the participants [70.76%; (n = 288/407)] had no knowledge of their partners’ status. Conclusion:Every pregnant woman should know their HIV status, disclose it to their sexual partners and know the status of their sexual partners as this will PMTCT, reduce HIV transmission and acquisition among sero- discordant couples.

Violence against women is a global challenge with negative health outcomes. Women living with HIV (WLHIV) in sero-discordant unions are at risk of violence after disclosure of their status. This st...

Poor adherence to antiretroviral therapy (ART) has significant consequences for adolescents. Conditional economic incentives (CEI) is an approach that may help address this challenge. This study evaluated the safety and preliminary efficacy of a group-based CEI program for ART adherence improvement among a sample of adolescents living in Ghana. A total of 35 adolescents (mean age: 14.7 years) on ART, though still with detectable viral load, were recruited from an HIV clinic and divided into 5 balanced groups to participate in peer-led group-based CEI activities during routine clinic visits. Four assessments were conducted across four visits at baseline and 3-, 6-, and 9-month follow-up, respectively. Main outcomes were ART adherence and viral load. Linear mixed models and thematic analysis were used for data analyses. The majority (91.4%) of the participants attended all four intervention activities. Participants reported missing an average of 1.06, 0.50, 0.91, 0.55 doses of ART in the past 7 days at baseline, 3-, 6-, and 9-month assessments, respectively. Most viral loads were ≥5,000 copies/ml at both baseline (68.6%) and 6-month assessments (54.3%). The incentive was divided between individual compensation for attending clinic and completing the assessment ($5 each, $20 in total) and a group-based compensation valued at $40 that was distributed during the 9-month assessment according to average group attendance (A≥90%, B≥75%, C≥60%, D

Background Viral suppression remains the most desired outcome in the management of patients with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) and this can be achieved by an effective combined Antiretroviral Therapy (cART). However, some patients who achieve viral suppression may experience viral rebound with dire consequence. We evaluated viral suppression and rebound and their associated factors among adult patients on cART in Kumasi, Ghana. Methods This hospital-based retrospective study was conducted at the Komfo Anokye Teaching Hospital in Ghana. We reviewed the medical records of 720 HIV patients on cART. Statistical analyses were performed using SPSS Version 26.0 and GraphPad prism version 8.0. Pp<0.0001], having good adherence to ART [aOR=5.64, 95%CI (2.86-11.13), pp=0.0260] and increasing duration of treatment (pppppp=0.004) and Zidovudine/Lamivudine/Nevirapine (aOR=18.68, 95% CI: 1.58-220.90; p=0.02) were independently associated with higher odds of viral rebound. Conclusion Approximately 76% viral suppression rate among HIV patients on cART in Kumasi falls below the WHO 95% target by the year 2030. Choice of ART combination, drug adherence, WHO clinical staging and baseline viral load are factors associated with suppression or rebound. These clinical characteristics of HIV patients must be monitored concurrently with the viral load.

Background Early initiation of breastfeeding (EIBF), breastfeeding within first hour after birth, is known to have major benefits for both the mother and newborn. EIBF rates, however, tends to vary between and within countries. This study set out to determine the prevalence of EIBF at the Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana, and to evaluate the determinants of EIBF and time to initiation of breastfeeding. Methods A cross-sectional study was conducted at the KATH postnatal wards between August and October 2014. Three hundred and eighty-two mothers delivering at KATH were recruited and data on time to initiation of breastfeeding, antenatal, delivery and immediate postnatal periods were collected. Data analyses using both binary and ordinal logistic regressions with stepwise elimination were used to determine the relationship between EIBF and time to initiation of breastfeeding on one side, and the maternal, pregnancy, delivery and neonatal associated factors. Results EIBF was done in 39.4% (95%CI: 34.3–44.5) of the newborns with breastfeeding initiated between 1 to 6 h for 19.7%, 6 to 11 h in 4.8%, 11 to 16 h in 4.8% and after 16 h in 28.5% of the deliveries. A higher number of antenatal care visits (AOR = 1.14, 95%CI: 1.04–1.25, p = 0.006), delivery by caesarean section (AOR = 0.07, 95%CI: 0.01–0.79, p = 0.031) and infant rooming-in with mother (AOR: 31.67, 95%CI: 5.59–179.43, p p = 0.039), Akan ethnicity (AOR = 1.92, 95%CI: 1.14–3.22, p = 0.014), first-born child (AOR = 2.06, 95%CI: 1.18–3.58, p = 0.011), mother rooming-in with newborn (AOR = 0.01. 95%CI: 0.00–0.02, p p = 0.010) and using prelacteals (AOR = 2.42, 95%CI: 1.34–4.40, p = 0.004). Conclusions The low EIBF rate and prolonged time to initiation of breastfeeding at a major tertiary health facility is a major concern. Key interventions will need to be implemented at KATH and possibly other tertiary healthcare facilities in Ghana and beyond to improve EIBF rate and time to breastfeeding.

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.

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.

Background: Family instability and partner conflicts are reportedly common in serodiscordant relationships. To date, the family adaptability, partnership, growth, affection and resolve (Family APGAR), a standardised tool for assessing family function, has not been used in any published literature involving this peculiar group. Aim: The aim of this study was to determine the predictors of family functionality and its association with human immunodeficiency virus (HIV) serodiscordance. Setting: The study was undertaken at the Kwame Nkrumah University of Science and Technology Hospital and Komfo Anokye Teaching Hospital in Kumasi, Ghana. Method: This was a cross-sectional study. A systematic sampling method was used to select HIV-positive clients whose partners were seropositive (concordant) or seronegative (discordant). A standardised format was used to extract relevant data. All data were analysed using STATA ® (version 14). Results were reported as odds ratios with 95% confidence intervals for study and outcome variables. Results: The study recruited 374 respondents, of which 52% (195) were in HIV-discordant relationships. Approximately 68% (254) of the respondents rated their families as functional, 15% (57) rated as moderately dysfunctional and 17% (63) rated as severely dysfunctional. A statistically significant relationship was found between family functionality and gender, as well as between family functionality and HIV status disclosure to the partner. No association was found between the Family APGAR and HIV serodiscordance. Conclusion: Amongst HIV couples, the strongest predictors of family functionality are gender and status disclosure. Healthcare providers should invest efforts into addressing gender-based challenges, utilise the Family APGAR and support disclosure of HIV status, especially amongst discordant couples.

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.

IFN-γ release assays (IGRAs) often present false-negative or indeterminate results in children with tuberculosis. HIV co-infection may contribute to decreased sensitivity of IGRAs by impairing T-cell IFN-γ expression. Measurement of alternative cytokines in QuantiFERON® (QFT) supernatants can circumvent the IFN-γ-dependency and may improve QFT sensitivity. We aimed to identify additional cytokines from QFT supernatants for detection of Mycobacterium tuberculosis infection in children with tuberculosis and HIV co-infection from Ghana. Concentrations of 18 cytokines in QFT supernatants from children (0–16 years) with tuberculosis concomitantly infected with HIV (n = 25) or without HIV (n = 24) from Ghana were measured using cytometric bead array (CBA). 29% of the children showed positive IFN-γ test results, and five cytokines, i.e., IL-6, IL-21, TNF-α, IL-1α and IP-10, detected M. tuberculosis infection with comparable or, for IL-6, with significantly higher sensitivity (59%). Increased age and HIV co-infection were associated with decreased cytokine induction, and especially IL-21 and IP-10 were less prevalent in HIV co-infected children with tuberculosis. Combined cytokine analyses increased proportions of positive tests, and a four-cytokine subset (i.e., IL-6, IL-21, IFN-γ, IL-1α) predicted 78% of the children with tuberculosis correctly. Combined evaluation of IFN-γ and alternative cytokines improved IGRA-sensitivity in children with tuberculosis.

Background: Anorectal malformations (ARMs) are congenital defects affecting the distal gastrointestinal tract and anus with frequent fistulous connections to the genitourinary system. The spectrum of the disease is considerably wide, and thus, an individualised approach to its management is required. There are few recent publications about the burden of this malformation in Africa and the outcome of surgical intervention. We present our experiences with the management of ARM, peculiar challenges and the outcome at a tertiary hospital catering for the Northern and Central parts of Ghana. Materials and Methods: This was a retrospective folder review of children with ARM at the Paediatric Surgical Unit of Komfo Anokye Teaching Hospital, Kumasi, Ghana, from 2011 to 2015. The data extracted included diagnosis, associated features, initial and definitive surgical treatment and post-operative complications. Results: Of the 53 records that were conclusively retrieved, the sex ratio was 1:1. The median age of presentation was 4.5 days (neonates), 4.5 months (infants) and 1.6 years (older children). There were 12 (44%) rectoperineal and 18 (69%) rectovestibular fistulas, representing the most common types of ARM in boys and girls, respectively. Posterior sagittal anorectoplasty and abdominoperineal pull-through were the corrective procedures performed. The overall complication rate was

Background Paediatric sepsis remains a major public health problem with significant morbidity and mortality especially in developing countries. Clinical symptoms associated with sepsis are unreliable and laboratory parameters unspecific, making an early diagnosis of paediatric sepsis difficult. The lack of definitive biomarker(s) for early diagnosis of sepsis further leads to the misuse of antibiotics. Diagnosis based on a single biomarker does not provide adequate accuracy. Subsequently, combining multiple biomarkers into a single score will help clinicians make a better diagnostic judgment. Aims This study for the first time evaluated the individual and combined diagnostic accuracy of procalcitonin (PCT), presepsin (sCD14-ST) and high sensitive C-reactive protein (hs-CRP) using a Bioscore model. Materials and methods In a case control study conducted at the Paediatric Emergency Unit (PEU) and the Mother and Baby Unit (MBU) of Komfo Anokye Teaching Hospital (KATH), sixty (60) paediatric subjects aged zero to six (0–6) years, were diagnosed with sepsis using case-definition by the national neonatal bloodstream infection surveillance and Pediatric Sepsis Consensus Congress. Thirty (30) other paediatric subjects, aged and sex matched without sepsis or inflammatory conditions were used as controls. One-time blood sample was taken at the time of admission for blood culture and measurement of PCT, hs-CRP, and presepsin by ELISA. The Statistical Package for Social Sciences (SPSS release 20.0, Copyright ©SPSS Inc.) was used for analysis. Results Out of the sixty septic paediatric subjects, 14 patients (23.3%) had positive blood cultures (LCS) and 46 (76%) had negative for blood cultures (CS). Klebsiella spp. recorded the highest median levels of PCT, and hs-CRP while Pseudo. Aeruginasa recorded the highest of sCD14-ST levels. Significant elevations in PCT, sCD14-ST and hs-CRP levels were observed among septic cases in comparison to controls (p < 0.0001). Individually, PCT showed better accuracy (AUC = 78.7%) followed by hs-CRP (AUC = 78.4%) and sCD14-ST (AUC = 74.8%). Combination of PCT + hs-CRP had the highest accuracy (AUC = 80.1%) followed by hs-CRP + sCD14-ST (AUC = 77.2%), PCT + sCD14-ST + hs-CRP (AUC = 77.0%) and PCT + sCD14-ST (AUC = 75.9%). Conclusion: hs-CRP, PCT, and sCD14-ST are independent predictors of paediatric sepsis due to their high prognostic values. Moreover, Bioscore combination of these biomarkers was significantly associated with increased odds for sepsis. The incorporation of these biomarkers into routine diagnostic tests will aid in prompt diagnosis of paediatric sepsis., Musculoskeletal system; Renal system; Infectious disease; Immunology; Reproductive system; Paediatrics; Paediatric sepsis; Presepsin; Procalcitonin; High sensitive C-reactive protein; Bioscore model.

Background: Children with chronic constipation dating to infancy frequently undergo rectal biopsy in order to rule out Hirschsprung's disease (HD) which is a common cause of this sort of presentation. Few publications have however focused on the documentation of the proportion of such patients who truly had histopathological findings confirming the disease. In this preliminary work, we aim to present the histopathological findings of children who had rectal biopsies in our centre from 2009 to 2014. Patients and Methods: A retrospective study was undertaken to review the histopathology reports of all rectal biopsies submitted to the Department of Pathology of the Komfo Anokye Teaching Hospital, Kumasi, from 2009 to 2014 on account of refractory constipation and suspected HD. Patient's biodata, clinical signs and symptoms were extracted from the request form. Results: Eighty-eight cases were seen during the study period with male to female ratio 2.8:1 and age range 6 months to 10 years. The modal age range is 24–36 months. Seventy-six of the specimens were adequate for histopathological assessment with 64 cases confirmed as HD while 12 cases were normal. Out of the confirmed cases, 3 cases showed absence of ganglion cells but no hypertrophy of nerve fibres. Conclusion: This preliminary work reveals that HD is rarely confirmed by biopsy in early infancy in our setting due to late presentation although the epidemiology of the disease is similar to that reported elsewhere.

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.)

Holding support groups with the same cohort of adolescents during clinic visits promises to increase engagement in care. Participants (N = 35 patients, aged 12-18, 50% female, from an adolescent HIV clinic in Kumasi, Ghana, were divided into 5 teams. Clinic visits were coordinated for members of each team. Team members participated in group discussions and activities while waiting to meet with their medical team. Teams met quarterly for 1 year. Participants reported benefits from talking with peers about the challenges of managing HIV. Clinic attendance improved from the preceding year (54% versus 84%). There were reductions in perceived internal stigma, perceived external stigma, worries about unintended disclosure from taking antiretroviral therapy (ART), and reduced ART concerns. The program demonstrated the feasibility, safety, and acceptability of facilitating increased interaction among adolescents living with HIV during clinic visits. Improvements in clinic attendance, perceived stigma, and concern about medications suggest that the intervention is a promising candidate for additional study.

We conducted a genome-wide association study of host resistance to severePlasmodium falciparummalaria in over 17,000 individuals from 11 malaria-endemic countries, undertaking a wide ranging analysis which identifies five replicable associations with genome-wide levels of evidence. Our findings include a newly implicated variant on chromosome 6 associated with risk of cerebral malaria, and the discovery of an erythroid-specific transcription start site underlying the association inATP2B4. Previously reported HLA associations cannot be replicated in this dataset. We estimate substantial heritability of severe malaria (h2~ 23%), of which around 10% is explained by the currently identified associations. Our dataset will provide a major building block for future research on the genetic determinants of disease in these diverse human populations.

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.)

Purpose Acute Respiratory Infection (ARI) is one of the topmost childhood killers ahead of diarrhoea and malnutrition in children. This exploratory qualitative study sought to examine the influence of maternal social constructs on the recognition and care seeking for fast breathing in children to inform the development of an intervention aimed at addressing fast breathing and acute respiratory infection related illness among children in Ghana. Method Focus group discussions with 23 mothers with children aged 6 weeks – 12 weeks old was conducted. The study used an abbreviated grounded theory and thus the full iterative cycle was not performed during the interview and data analysis. Results Fast breathing is locally called ‘oteeso’(difficulty in breathing), and ‘mframa-ko-ne-mu’(air has entered the child). Evil spirit, heredity, and exposure to windy weather were mentioned as the causes. Herbs and herbal preparations are perceived to be more effective in managing fast breathing. Mothers have varying construction of causes, presentation and treatment options for fast breathing, and these have implications in control and prevention. Conclusion Understanding the local construction of illness beliefs is key to designing interventions aimed at empowering mothers to seek early care for their children on respiratory related illness.

Increased accessibility to Antiretroviral Therapy (ART) has resulted in the decline of deaths among children with Perinatally Infected Human Immunodeficiency Virus (PIHIV). Their adherence to Highly Active ART (HAART) is vital for their survival and quality of life. This study aimed at determining HAART medication adherence among adolescents with PIHIV. The study was cross-sectional conducted from September 2015 to January 2016 at a teaching hospital in Ghana. It involved 106 adolescents aged 10-20 years. Morisky's eight-item medication adherence scale was adapted and used to determine the adherence level. Factors influencing adherence were also determined by interviewing the adolescents. EpiData 3.1 and Stata version 12 were used for data entry and analysis respectively. There was low adherence in 76.4% of the adolescents, and the HAART regimen associated with high medication adherence was tenofovir, lamivudine and efavirenz combinations (p = .011). Forgetfulness (p = .001) and inability to come for refill (p = .013) were the main factors associated with low adherence. However adherence was not significantly associated with a lack of medication supply or stigmatization. Addressing the modifiable factors found in this study to be associated with low adherence are essential interventions for their long-term quality of life.

Background: The Expanded Programme on Immunization (EPI), since its inception in 1974, has helped avert about 2-3 million deaths annually. In Ghana, there is inadequate information on the transition from knowledge acquired in the classroom to practice among vaccinators. This study seeks to provide evidence on the level of knowledge and competencies of vaccinators in Ghana. Method: A prospective cross-sectional study with consecutive sampling technique was employed to select 110 eligible subjects from health facilities in two districts in the Ashanti region of Ghana. Data were collected in real time using standardised tools, uploaded on the Open Data Kit (ODK), and subsequently exported to STATA 13.0 for statistical analysis. Results: Seventy two percent (72.73%) of respondents were from urban health facilities. Community Health Nurses constituted majority of respondents 83.09%. Sixty-five percent (65.46%) of participants had less than five years’ experience in vaccination. BCG was correctly identified by 91.82% of respondents as a single dose vaccine and yellow fever by 89.09%. Pentavalent, rotavirus and pneumococcal vaccine were correctly identified by 91.82%, 82.73% and 82.73% respectively as multiple dose vaccines. Ninety seven percent (97.27%) of respondents correctly mentioned pentavalent as having its first dose administered at 6 weeks. 98.18% correctly indicated pentavalent and pneumococcal as given intramuscularly whereas 92.27% identified OPV and rotavirus as given orally. Eighty-eight percent (88.18%) of respondents knew vaccine temperature charting is required twice a day. Conclusion: The study revealed gaps in the principles of vaccine handling and administration. A critical need for routine assessment and refresher training for population where vaccination is conducted by different level of training.

Tuberculosis (TB) is a major cause of human mortality particularly in association with the human immunodeficiency virus (HIV). Nocardia spp. has emerged as an opportunistic infection especially in HIV patients. The high prevalence of TB and HIV coupled with the lack of a definitive laboratory diagnosis for Nocardia spp. could lead to misdiagnosed pulmonary TB. This study determined the prevalence of pulmonary infections due to Nocardia spp. and Mycobacterium tuberculosis in sputum of HIV and non-HIV patients with suspected pulmonary tuberculosis at KATH. A total of sixty sputum samples were obtained from HIV and non-HIV patients with suspected pulmonary tuberculosis. Samples were examined by fluorescence based Ziehl–Neelsen staining, culture, and PCR methods. The prevalence of Nocardia spp. and Mycobacterium tuberculosis was 18.3% and 20%, respectively, with the latter having the highest rate among patients aged 21–40 years (P=0.075). The prevalence of Nocardia spp. among HIV patients was 90.9% whilst 16.7% of the patients had HIV/Nocardia spp. coinfection. Detection of Mycobacterium tuberculosis by fluorescence-based Ziehl–Neelsen staining, culture, and PCR yielded 9 (15%), 11 (18.3%), and 12 (20%), respectively. There is a high prevalence of nocardiosis especially in HIV patients. PCR is a better diagnostic method that detects both Nocardia spp. and Mycobacterium tuberculosis and should be incorporated into routine diagnosis for pulmonary infections.

Adolescents with perinatally acquired HIV seem to be most stigmatized. There is a need to put together policies to enable them cope with the burden and live fruitful lives. In Ghana, a group of activities and rewards are being put in place to aid in helping these teens cope with the stigma.

Objective. This study sought to describe the trend of sputum organism density and the rate of bacteriological conversion among smear positive TB patients assessing care at the Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana. Methods. We conducted a retrospective patient folder review from January 2013 to March 2016 at the KATH, a tertiary hospital in Ghana. The data was entered into Microsoft Access database and exported into STATA for analysis. We applied basic descriptive statistics to study variables. Sputum conversion rate (SCR) was estimated using the number of negative tests recorded over a period (numerator) and the number of patients reported in the same period (denominator) and expressed as a percentage. Results. A total of 278 patient records with sputum smear positive at onset were studied. Before treatment sputum density detected in smear microscopy was as follows: 1 acid-fast bacillus (+) (n=114), scanty (n=19), ++ (n=67), and +++ (n=78). We recorded sputum conversion rate of 80.90%, 94.56%, and 98.31% in the intensive, continuation, and completion phases, respectively. Conclusion. This study has shown an increasing trend in sputum conversion of smear positive pulmonary tuberculosis and an increasing trend in loss to follow-ups among tuberculosis patients on treatment.

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.)

Many human genetic associations with resistance to malaria have been reported, but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. We tested 55 SNPs in 27 loci previously reported to associate with severe malaria. There was evidence of association at P < 1 × 10(-4) with the HBB, ABO, ATP2B4, G6PD and CD40LG loci, but previously reported associations at 22 other loci did not replicate in the multicenter analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, with a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed.

Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a collection of 48 sub-Saharan African groups. We show that coastal populations experienced an influx of Eurasian haplotypes over the last 7000 years, and that Eastern and Southern Niger-Congo speaking groups share ancestry with Central West Africans as a result of recent population expansions. In fact, most sub-Saharan populations share ancestry with groups from outside of their current geographic region as a result of gene-flow within the last 4000 years. Our in-depth analysis provides insight into haplotype sharing across different ethno-linguistic groups and the recent movement of alleles into new environments, both of which are relevant to studies of genetic epidemiology. DOI: http://dx.doi.org/10.7554/eLife.15266.001, eLife digest Our genomes contain a record of historical events. This is because when groups of people are separated for generations, the DNA sequence in the two groups’ genomes will change in different ways. Looking at the differences in the genomes of people from the same population can help researchers to understand and reconstruct the historical interactions that brought their ancestors together. The mixing of two populations that were previously separate is known as admixture. Africa as a continent has few written records of its history. This means that it is somewhat unknown which important movements of people in the past generated the populations found in modern-day Africa. Busby et al. have now attempted to use DNA to look into this and reconstruct the last 4000 years of genetic history in African populations. As has been shown in other regions of the world, the new analysis showed that all African populations are the result of historical admixture events. However, Busby et al. could characterize these events to unprecedented level of detail. For example, multiple ethnic groups from The Gambia and Mali all show signs of sharing the same set of ancestors from West Africa, Europe and Asia who mixed around 2000 years ago. Evidence of a migration of people from Central West Africa, known as the Bantu expansion, could also be detected, and was shown to carry genes to the south and east. An important next step will be to now look at the consequences of the observed gene-flow, and ask if it has contributed to spreading beneficial, or detrimental, mutations around Africa. DOI: http://dx.doi.org/10.7554/eLife.15266.002

In Sub-Saharan Africa, increasing numbers of children with perinatally acquired HIV (PAHIV) are living into adolescence. These adolescents face numerous unique challenges such as parent illness/death and years of medication use. Optimizing care for these youth requires an understanding of the factors that contribute to physical health, psychological wellbeing, social relationships, and quality of life. This mixed methods study collected quantitative questionnaire data from 40 Ghanaian adolescents with PAHIV (50% female, 12–19 years old) who received care through an adolescent HIV clinic in Kumasi, Ghana. The study also presents results from qualitative interviews conducted with 20 adolescents. Results from quantitative analyses suggested that a significant number of participants were not virally suppressed (67%) and participants reported barriers to treatment adherence, limited social support, concerns about disclosure and HIV-related stigma, limited resources, and lower than expected quality of life (QOL). Salient themes from the qualitative analyses included limited understanding of how HIV is transmitted, the interplay between food insecurity and treatment adherence and the need for developing safe relationships through which adolescents can discuss their illness without fear of accidental disclosure of their HIV status.

The majority of HIV-infected children in sub-Saharan Africa have not been informed of their HIV status. Caregivers are reluctant to disclose HIV status to their children because of concern about the child's ability to understand, parental sense of guilt, and fear of social rejection and isolation. We hypothesized that the low prevalence of pediatric HIV disclosure in Ghana is due to lack of accurate HIV information and high HIV stigma among caregivers. This is a preliminary analysis of baseline data of an HIV pediatric disclosure intervention study in Ghana ("Sankofa"). "Sankofa" - is a two-arm randomized controlled clinical trial comparing disclosure intervention plus usual care (intervention arm) vs usual care (control arm) at Korle-Bu Teaching Hospital (KBTH; control arm) and Komfo-Anokye Teaching Hospital (KATH; intervention arm). We enrolled HIV-infected children, ages 7-18 years who do not know their HIV status, and their caregivers. Baseline data of caregivers included demographic characteristics; Brief HIV Knowledge Questionnaire (HIV-KQ-18); Brief Illness Perception Questionnaire; and HIV Stigma Scale. Simple and multivariable linear regression analyses were used to assess the relationship between caregiver characteristics and HIV knowledge, stigma, and illness perception. Two hundred and ninety-eight caregivers were enrolled between January 2013 and July 2014 at the two study sites; KBTH (n = 167) and KATH (n = 131). The median age of caregivers was 41 years; 80.5% of them were female and about 60% of caregivers were HIV-positive. Seventy-eight percent of caregivers were self-employed with low household income. In both unadjusted and adjusted analyses, HIV negative status and lower level of education were associated with poor scores on HIV-KQ. HIV positive status remained significant for higher level of stigma in the adjusted analyses. None of the caregiver's characteristics predicted caregiver's illness perception. Intensification of HIV education in schools and targeted community campaigns are needed.

With the scale-up of effective antiretroviral therapy in resource-limited settings, many HIV-infected children are now able to survive into adulthood. To achieve this potential, children must navigate normative developmental processes and challenges while living with an unusually complex, stigmatizing, potentially fatal chronic illness and meeting the demands of treatment.Yet many of these children, especially preadolescents, do not know they are HIV-infected. Despite compelling evidence supporting the merits of informing children of their HIV status, there has been little emphasis on equipping the child's caregiver with information and skills to promote disclosure, particularly, when the caregiver faces a variety of sociocultural barriers and is reluctant to do so. In this study, we present the background, process and methods for a first of its kind collaboration that is examining the efficacy of an intervention developed to facilitate the engagement of caregivers in the process of disclosure in a manner suitable to the sociocultural context and developmental age and needs of the child in Ghana. We also report preliminary data that supported the design of the intervention approach and currently available domains of the data system. Finally, we discuss challenges and implications for future research.

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.

Objective To evaluate hearing loss in children as a complication of sickle-cell disease. Methods In Kumasi, Ghana, 35 children with SCD aged 6 months to 10 years underwent transient-evoked otoacoustic emissions testing (TEOAE) to investigate the function of the inner ear. Healthy Ghanaian children recruited in school and kindergarten served as controls. Results One of 35 children with SCD and 13 of 115 control children failed the otoacoustic emissions testing. This difference between the control group and the children with SCD was not statistically significant. Conclusion Early hearing impairment does not regularly occur in sickle-cell disease, and in children, it is not a likely cause of delayed or impaired language development. Objectif Evaluer la perte auditive chez les enfants suite a une complication de la drepanocytose. Methodes A Kumasi, au Ghana, 35 enfants atteints de drepanocytose âges de 6 mois a 10 ans ont subi un test transitoire evoque d'otoemissions acoustique afin d'investiguer la fonction de l'oreille interne. Des enfants ghaneens sains recrutes a l’ecole et a la maternelle ont servi de temoins. Resultats Un des 35 enfants drepanocytaires et 13 de 115 enfants temoins ont echoue au test d'otoemission acoustique. Cette difference entre le groupe temoin et les enfants drepanocytaires n’etait pas statistiquement significative. Conclusion La deficience auditive precoce ne survient pas regulierement dans la drepanocytose; et chez les enfants, elle n'est pas une cause probable de retard ou de deficience du developpement du langage. Objetivo Evaluar la perdida auditiva en ninos como complicacion de la anemia falciforme (AF). Metodos A 35 ninos con AF y edades entre los 6 meses y 10 anos se les realizo una evaluacion de emisiones otoacusticas evocadas transitorias (EOET) para investigar la funcion del oido interno, en Kumasi, Ghana. Ninos Ghaneses sanos, reclutados en la escuela primaria y preescolar, sirvieron como controles. Resultados Uno de 35 ninos con AF y 13 de los 115 controles fallaron las pruebas de emisiones otoacusticas. Esta diferencia entre el grupo control y los ninos con AF no era estadisticamente significativa. Conclusion La perdida auditiva temprana no suele ocurrir de forma regular en la anemia falciforme; y en ninos no parece ser la causa de un retraso o disfuncion en el desarrollo del lenguaje.

Background An unprecedented global effort at scaling up universal access to antiretroviral therapy has decreased the progression of HIV. However, due to challenges with supplies and adherence to intermittent antiretroviral therapy (ART) for mothers, infants continue to be infected, some with resistant viruses. Exposure to these resistant strains leads to non-responsiveness to therapy resulting in virological failure. Children are more vulnerable to HIV drug resistance because of their life long treatment, the possible selection of resistant strains as a result of prophylaxis for mothers with HIV enrolled in PMTCT. The objective of the study was to determine the prevalence and risk factors of virological resistance among HIV-1-positive children on antiretroviral therapy. Methods This was a longitudinal study that was performed at the HIV paediatric clinic of the Komfo Anokye Teaching Hospital, Kumasi, Ghana. Blood samples of children below the age of 18 years who had been on therapy for at least 3 months were analysed for virological load using real-time COBAS AmpliPrep/COBAS Taqman PCR. The samples were analysed at two consecutive time points when they came for their ART refill. Socio-demographic and clinical information was collected from their folders and also from the mother. Results A total of 188 subjects were enrolled into the study from September 2015 to June 2016. The average duration on ART was 36 months (IQR=12–72 months). Of all subjects recruited, 134 (71.3%) were found to be on regular drug ART. Of these, 21 (15.7%) had virological failure and 102 (76.1%) had virological suppression. A regression analysis showed that subjects whose parents were unemployed had 5.4 (1.4–20.9) chances of virological failure compared to those with parents employed. Conclusions The risk of virological failure among HIV-positive children is still high. Efforts must be made to further identify the potential causes of virological failure among these children.

To the Editor: The directly observed treatment strategy (DOTS) for tuberculosis (TB) treatment has been implemented in Ghana since 1994. Before then, TB was treated without adherence to any concerted guidelines. The 2003 report of the Ghanaian National Tuberculosis Programme (NTP) stated a TB incidence of 281/100,000 (1). NTP ensures treatment of all patients with an 8-month course of streptomycin, isoniazid, rifampin, and pyrazinamide (for 2 months), followed by thiacetazone and isoniazid (6 months). The cure rate for 2003 was >50% (1), and >75% is anticipated for 2005. To determine the extent of drug resistance and to make suggestions for future Ghanaian NTP strategies, we assessed resistance against anti-TB drugs used in Ghana. A total of 2,064 patients with new cases of pulmonary TB were recruited at Korle Bu Teaching Hospital, Accra; Komfo Anokye Teaching Hospital, Kumasi; 15 periurban hospitals; and hospitals in the Ashanti, Eastern, and Central Regions of Ghana. These patients were consecutively enrolled in a cross-sectional study from September 2001 to December 2004. On all patients’ clinical examinations, chest radiographs, sputum smears for staining of acid-fast bacteria, HIV testing, and culturing of Mycobacterium tuberculosis complex strains were performed. Samples were taken only after informed consent was given. The study was approved by the appropriate ethics committees. A total of 2,064 Mycobacterium isolates were cultured at the Kumasi Centre for Collaborative Research. After decontamination of sputum samples (N-acetyl-L-cysteine/NaOH) and centrifugation, sediments were transferred onto Lowenstein-Jensen (LJ) media, incubated (37°C), and read weekly for 10 weeks for mycobacterial growth. Subsequently, cultures were sent to the German National Reference Centre for Mycobacteria in Borstel, Germany, a reference laboratory of the World Health Organization, for drug sensitivity testing (DST; proportion method on LJ media). Sensitivity to isoniazid, rifampin, pyrazinamide, ethambutol, and streptomycin was determined for 2,064 isolates and to thiacetazone for 1,288 isolates. For ambiguous results and DST of thiacetazone, the modified proportion method (Bactec 460TB; Becton Dickinson, Cockeysville, MD, USA) was performed. Data were analyzed with EpiInfo (Centers for Disease Control and Prevention, Atlanta, GA, USA) and Fourth Dimension (ACI Group, San Jose, CA, USA) software programs. Of the isolates, 32.8% were from female patients, and 67.8% were from male patients. The mean age of participants (33 years, range 10–60) did not differ by sex. HIV prevalence was 14.3% (males, n = 179, females, n = 117). A total of 1,578 (76.5%) isolates were susceptible to all drugs tested, whereas 304 (14.7%) were monodrug resistant, and 177 (8.7%) were multi- or polydrug resistant to combinations (multidrug resistance meant resistance to at least isoniazid and rifampin (2.2%); polydrug resistance meant resistance to several drugs, excluding combined resistance to isoniazid and rifampin (6.5%). The overall prevalence of any drug resistance was 23.5% (486 isolates) (Table). No differences were observed between HIV-negative and HIV-positive patients. The highest level of resistance was against streptomycin, followed by isoniazid. Resistance to rifampin, pyrazinamide, and thiacetazone was lower. Monoresistance to ethambutol was not observed; resistance to ethambutol combined with other drugs occurred in 0.9% of isolates. Table Resistance to first-line antituberculosis drugs, Ghana* In all, 6.5% of isolates were polydrug resistant and virtually always included resistance to isoniazid. Among isolates with double- and triple drug resistance, combinations of resistance to isoniazid and streptomycin and to isoniazid-thiacetazone-streptomycin occurred most frequently. Other combinations were relatively rare. In 1989, an initial drug resistance rate of 54.5% in pulmonary TB was observed in Ghana (2); 27% were resistant to isoniazid, 23% to streptomycin, 29% to thiacetazone, 16% to streptomycin-isoniazid, and 5% to thiacetazone-streptomycin-isoniazid. A later study reported a high prevalence of primary drug resistance to isoniazid (23%), while sensitivity to rifampicin, pyrazinamide, ethambutol, streptomycin, and ciprofloxacin was maintained (3). However, the number of isolates tested was fewer in both studies (n = 99 and 25, respectively) than in ours. This report supplements data from patients in Ghana whose conditions were newly diagnosed as HIV-negative and HIV-positive. Samples were collected in 2 large regions of Ghana, the Greater Accra and the Ashanti Regions, and were supplemented by samples from additional regions. Thus, these results are likely representative of the entire country. The overall primary drug resistance rate of 23.5% in Ghanaian TB patients ranks Ghana among those African countries with a high prevalence of drug-resistant TB. The high degree of mono-, multi- and polyresistance to streptomycin may be the result of selective pressure exerted by treatment of other infections with streptomycin and to incomplete treatment courses. Drug resistance to streptomycin and isoniazid are of concern, since these drugs are core components of the NTP. The relative ineffectiveness of streptomycin and the low level of resistance to ethambutol justify the most recent replacement of streptomycin by ethambutol by the Ghanaian NTP. Low rates of initial drug resistance have been reported in countries in which the DOTS strategy has been successfully implemented. Adequate use of standardized treatment regimens under DOTS will limit further emergence of drug resistance but not substantially reduce the current degree of resistance (4). Although the levels of drug resistance in Africa are lower than in several other countries (5), measures to provide controlled application of second-line drugs, supervision of drug distribution and compliance, enforcement of DOTS protocols, and sustained training of all personnel involved in TB management are crucial.

Structural variants of the Mannose Binding Lectin (MBL) cause quantitative and qualitative functional deficiencies, which are associated with various patterns of susceptibility to infectious diseases and other disorders. We determined genetic MBL variants in 2010 Ghanaian patients with pulmonary tuberculosis (TB) and 2346 controls and characterized the mycobacterial isolates of the patients. Assuming a recessive mode of inheritance, we found a protective association between TB and the MBL2 G57E variant (odds ratio 0.60, confidence interval 0.4-0.9, P 0.008) and the corresponding LYQC haplotype (P(corrected) 0.007) which applied, however, only to TB caused by M. africanum but not to TB caused by M. tuberculosis. In vitro, M. africanum isolates bound recombinant human MBL more efficiently than did isolates of M. tuberculosis. We conclude that MBL binding may facilitate the uptake of M. africanum by macrophages, thereby promoting infection and that selection by TB may have favoured the spread of functional MBL deficiencies in regions endemic for M. africanum.

Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are scientific, ethical and practical challenges to carrying out such studies in developing countries, where the burden of disease is greatest. The Malaria Genomic Epidemiology Network (MalariaGEN) is now working to overcome these obstacles, using a consortial approach that brings together researchers from 21 countries. © 2008 Macmillan Publishers Limited. All rights reserved.

The human immunity-related GTPase M (IRGM) has been shown to be critically involved in regulating autophagy as a means of disposing cytosolic cellular structures and of reducing the growth of intracellular pathogens in vitro. This includes Mycobacterium tuberculosis, which is in agreement with findings indicating that M. tuberculosis translocates from the phagolysosome into the cytosol of infected cells, where it becomes exposed to autophagy. To test whether IRGM plays a role in human infection, we studied IRGM gene variants in 2010 patients with pulmonary tuberculosis (TB) and 2346 unaffected controls. Mycobacterial clades were classified by spoligotyping, IS6110 fingerprinting and genotyping of the pks1/15 deletion. The IRGM genotype −261TT was negatively associated with TB caused by M. tuberculosis (OR 0.66, CI 0.52–0.84, Pnominal 0.0009, Pcorrected 0.0045) and not with TB caused by M. africanum or M. bovis (OR 0.95, CI 0.70–1.30. P 0.8). Further stratification for mycobacterial clades revealed that the protective effect applied only to M. tuberculosis strains with a damaged pks1/15 gene which is characteristic for the Euro-American (EUAM) subgroup of M. tuberculosis (OR 0.63, CI 0.49–0.81, Pnominal 0.0004, Pcorrected 0.0019). Our results, including those of luciferase reporter gene assays with the IRGM variants −261C and −261T, suggest a role for IRGM and autophagy in protection of humans against natural infection with M. tuberculosis EUAM clades. Moreover, they support in vitro findings indicating that TB lineages capable of producing a distinct mycobacterial phenolic glycolipid that occurs exclusively in strains with an intact pks1/15 gene inhibit innate immune responses in which IRGM contributes to the control of autophagy. Finally, they raise the possibility that the increased frequency of the IRGM −261TT genotype may have contributed to the establishment of M. africanum as a pathogen in the West African population., Author Summary Autophagy is a process in which cell components are degraded by the lysosomal machinery. It has recently been described that activation of autophagy reduces the viability of M. tuberculosis in phagosomes due to an intimate autophagy-phagocytosis interaction. M. tuberculosis may also be directly accessible to autophagy, as M. tuberculosis was found to translocate into the cytoplasm. The immunity-related GTPase IRGM is a mediator of innate immune responses and induces autophagy. We have studied genetic variants of the human IRGM gene in a Ghanaian tuberculosis case-control group and found that the IRGM variant −261T provides relative protection against disease when the infection is caused by the Euro-American lineage of M. tuberculosis. This lineage is characterized by the pks1/15 seven base-pair (bp) deletion. The product of an intact pks1/15 gene, phenolic glycolipid-tb, might contribute to mycobacterial virulence by suppressing innate immune responses. It is, therefore, conceivable that only the Euro-American lineage is exposed to IRGM-triggered innate defence mechanisms. Our observations suggest that the increased frequency of the IRGM −261TT genotype may have allowed the establishment of M. africanum as a pathogen in West Africa.