Epidemiologic and viral predictors of antiretroviral drug resistance among persons living with HIV in a large treatment program in Nigeria.

BACKGROUND: Expanded access to combination antiretroviral therapy (cART) throughout sub-Saharan Africa over the last decade has remarkably improved the prognosis of persons living with HIV (PLWH). However, some PLWH experience virologic rebound after a period of viral suppression, usually followed by selection of drug resistant virus. Determining factors associated with drug resistance can inform patient management and healthcare policies, particularly in resource-limited settings where drug resistance testing is not routine. METHODS: A case-control study was conducted using data captured from an electronic medical record in a large treatment program in Nigeria. Cases PLWH receiving cART who developed acquired drug resistance (ADR) and controls were those without ADR between 2004 and 2011. Each case was matched to up to 2 controls by sex, age, and education. Logistic regression was used estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with ADR. RESULTS: We evaluated 159 cases with ADR and 299 controls without ADR. In a multivariate model, factors associated with ADR included older age (OR = 2.35 [age 30-40 years 95% CI 1.29, 4.27], age 41 + years OR = 2.31 [95% CI 1.11, 4.84], compared to age 17-30), higher education level (secondary OR 2.14 [95% CI 1.1.11-4.13]), compared to primary and tertiary), non-adherence to care (OR = 2.48 [95% CI 1.50-4.00]), longer treatment duration (OR = 1.80 [95% CI 1.37-2.35]), lower CD4 count((OR = 0.95 [95% CI 0.95-0.97]) and higher viral load (OR = 1.97 [95% CI 1.44-2.54]). CONCLUSIONS: Understanding these predictors may guide programs in developing interventions to identify patients at risk of developing ADR and implementing prevention strategies.

Population attributable risk of key modifiable risk factors associated with non-exclusive breastfeeding in Nigeria.

BACKGROUND: Non-exclusive breastfeeding (non-EBF) is a risk factor for many of the 2300 under-five deaths occurring daily in Nigeria - a developing country with approximately 40 million children. This study aimed to quantify and compare the attributable burden of key modifiable risk factors associated with non-EBF in Nigeria to inform strategic policy responses and initiatives. METHODS: Relative risk and exposure prevalence for selected modifiable risk factors were used to calculate population attributable fractions based on Nigeria Demographic and Health Surveys data for the period (1999-2013). Scenarios based on feasible impact of community-based interventions in reducing exposure prevalence were also considered to calculate comparative potential impact fractions. RESULTS: In Nigeria, an estimated 22.8% (95% Confidence Interval, CI: 9.2-37.0%) of non-EBF was attributable to primary and no maternal education; 24.7% (95% CI: 9.5-39.5%) to middle and poor household wealth, 9.7% (1.7-18.1%) to lower number (1-3) and no antenatal care visits; 18.8% (95% CI: 6.9-30.8%) to home delivery and 16.6% (95% CI: 3.0-31.3%) to delivery assisted by a non-health professional. In combination, more than half of all cases of non-EBF (64.5%; 95% CI: 50.0-76.4%) could be attributed to those modifiable risk factors. Scenarios based on feasible impacts of community-based approaches to improve health service access and human capacity suggest that an avoidable burden of non-EBF practice of approximately 11% (95% CI: -5.4; 24.7) is achievable. CONCLUSION: Key modifiable risk factors contribute significantly to non-EBF in Nigerian women. Community-based initiatives and appropriate socio-economic government policies that specifically consider those modifiable risk factors could substantially reduce non-EBF practice in Nigeria.

Gaps and strategies in developing health research capacity: experience from the Nigeria Implementation Science Alliance.

BACKGROUND: Despite being disproportionately burdened by preventable diseases than more advanced countries, low- and middle-income countries (LMICs) continue to trail behind other parts of the world in the number, quality and impact of scholarly activities by their health researchers. Our strategy at the Nigerian Implementation Science Alliance (NISA) is to utilise innovative platforms that catalyse collaboration, enhance communication between different stakeholders, and promote the uptake of evidence-based interventions in improving healthcare delivery. This article reports on findings from a structured group exercise conducted at the 2016 NISA Conference to identify (1) gaps in developing research capacity and (2) potential strategies to address these gaps. METHODS: A 1-hour structured group exercise was conducted with 15 groups of 2-9 individuals (n = 94) to brainstorm gaps for implementation, strategies to address gaps and to rank their top 3 in each category. Qualitative thematic analysis was used. First, duplicate responses were merged and analyses identified emerging themes. Each of the gaps and strategies identified were categorised as falling into the purview of policy-makers, researchers, implementing partners or multiple groups. RESULTS: Participating stakeholders identified 98 gaps and 91 strategies related to increasing research capacity in Nigeria. A total of 45 gaps and an equal number of strategies were ranked; 39 gaps and 43 strategies were then analysed, from which 8 recurring themes emerged for gaps (lack of sufficient funding, poor research focus in education, inadequate mentorship and training, inadequate research infrastructure, lack of collaboration between researchers, research-policy dissonance, lack of motivation for research, lack of leadership buy-in for research) and 7 themes emerged for strategies (increased funding for research, improved research education, improved mentorship and training, improved infrastructure for research, increased collaboration between academic/research institutions, greater engagement between researchers and policy-makers, greater leadership buy-in for research). CONCLUSIONS: The gaps and strategies identified in this study represent pathways judged to be important in increasing research and implementation science capacity in Nigeria. The inclusion of perspectives and involvement of stakeholders who play different roles in policy, research and implementation activities makes these findings comprehensive, relevant and actionable, not only in Nigeria but in other similar LMICs.

A Decade of Monitoring HIV Epidemics in Nigeria: Positioning for Post-2015 Agenda.

BACKGROUND: Nigeria accounts for 9% of the global HIV burden and is a signatory to Millennium Development Goals as well as the post-2015 Sustainable Development Goals. This paper reviews maturation of her HIV M&E system and preparedness for monitoring of the post-2015 agenda. METHODS: Using the UNAIDS criteria for assessing a functional M&E system, a mixed-methods approach of desk review and expert consultations, was employed. RESULTS: Following adoption of a multi-sectoral M&E system, Nigeria experienced improved HIV coordination at the National and State levels, capacity building for epidemic appraisals, spectrum estimation and routine data quality assessments. National data and systems audit processes were instituted which informed harmonization of tools and indicators. The M&E achievements of the HIV response enhanced performance of the National Health Management Information System (NHMIS) using DHIS2 platform following its re-introduction by the Federal Ministry of Health, and also enabled decentralization of data management to the periphery. CONCLUSION: A decade of implementing National HIV M&E framework in Nigeria and the recent adoption of the DHIS2 provides a strong base for monitoring the Post 2015 agenda. There is however a need to strengthen inter-sectoral data linkages and reduce the rising burden of data collection at the global level.

Drug resistance patterns following pharmacy stock shortage in Nigerian Antiretroviral Treatment Program.

BACKGROUND: For patients on antiretroviral therapy (ART), treatment interruptions can impact patient outcomes and result in the accumulation of drug resistance mutations leading to virologic failure. There are minimal published data on the impact of an ART stock shortage on development of drug resistance mutations (DRMs). In this report, we evaluate data from patients enrolled in the Government of Nigeria National ART Program that were receiving treatment at the time of a national drug shortage in late 2003. METHODS: We conducted a cross-sectional evaluation of samples collected between December 2004 and August 2005 from ART patients in virologic failure that either had a treatment interruption or did not during the late 2003 drug shortage period at the Jos University Teaching Hospital (JUTH). Plasma virus was genotyped, sequence data were edited and analyzed, and mutation profiles were categorized to evaluate predicted drug susceptibility. Data were analyzed to examine factors associated with development of resistance mutations. A genotypic sensitivity score to the alternate recommended regimen was computed to assess drug susceptibility if regimens were changed. RESULTS: A total of 56 patients were included in this evaluation (28 interrupted, 28 uninterrupted). Patients in the interrupted group had more DRMs than those in the uninterrupted group (p < 0.001); interrupted patients were more likely than uninterrupted patients to have one or more TAM-2 mutations (57.1% interrupted vs. 21.3% uninterrupted; p = 0.04). There was a statistically significant difference in resistance to both d4T (53.7% interrupted vs. 17.9 uninterrupted; p = 0.011) and AZT (64.3% interrupted vs. 25.0% uninterrupted; p = 0.003) by drug interruption status. Examining genotypic sensitivity scores, we found that 67.9% of the interrupted patients, as compared to 25.0% of the uninterrupted patients, did not have full susceptibility to one drug in the regimen to which guidelines recommended they be switched (p = 0.001). DISCUSSION: In this small observational study, we found evidence of a difference in resistance profiles and ART susceptibility between those that were stocked-out of drug versus those that were not. We believe that these data are relevant for many other low- and middle-income countries (LMIC) that also experienced similar ART shortages as they rapidly scaled up their national programs.

Evaluation of gene xpert for routine diagnosis of HIV-associated tuberculosis in Nigeria: A prospective cohort study.

BACKGROUND: Xpert MTB/Rif (Xpert) is described as a game changer in tuberculosis (TB) control. We evaluated the impact of Xpert on diagnosis, time to treatment, and treatment outcome among patients with HIV associated TB in Nigeria. METHODS: Adults with HIV being evaluated for pulmonary TB (PTB) were consecutively enrolled into the study cohort. At baseline, expectorated sputa were examined using Xpert and smear microscopy for Mycobacterium tuberculosis (MTB) and acid fast bacilli, respectively. Patients diagnosed with TB were followed-up until 6 months post TB diagnosis. TB was defined as sputum positive by smear microscopy, Xpert detection of MTB (bacteriologically confirmed case), or clinician diagnosed TB with initiation of full TB treatment (clinical diagnosis). Time to treatment was time from first clinic presentation for TB evaluation to initiation of TB treatment. We examined the proportion PTB patients with a positive Xpert result and compared time to TB treatment and outcome of TB treatment in patients based on sputum test results. RESULTS: A total of 310 adults with HIV were enrolled. The median CD4 cell count was 242 (interquartile range (IQR) 120-425) cells/mm3 and 88.1% were receiving antiretroviral therapy (ART). PTB was diagnosed in 76 (24.5%) patients, with 71 (93.4%) being bacteriologically confirmed. Among patients with PTB, 56 (73.7%) were Xpert positive. Median time to treatment was 5 (IQR 2-8) days and 12 (IQR 5-35) days in patient with and without Xpert positive results, respectively; p = 0.005. Overall 73.1% had symptom free survival at 6 months post PTB treatment initiation with no significant differences observed based on TB test method. 10 (14.9%) died within 6 months of TB treatment initiation. In analysis adjusted for age, sex, and mode of diagnosis (Xpert positive or negative), only ART use independently predicted mortality (AOR 0.10; 95% CI 0.01-0.93). CONCLUSION: The use of Xpert for routine care reduced time to PTB treatment, but did not improve survival in patients with HIV treated for susceptible PTB.

Assessment of provider-initiated HIV screening in Nigeria with sub-Saharan African comparison.

BACKGROUND: Despite Nigeria's high HIV prevalence, voluntary testing and counselling rates remain low. UNAIDS/WHO/CDC recommends provider-initiated testing and counselling (PITC) for HIV in settings with high HIV prevalence. We aimed to assess the acceptability and logistical feasibility of the PITC strategy among adolescents and adults in a secondary health care centre in Idekpa Benue state, Nigeria. METHOD: All patients (aged ≥ 13 years) who visited the out-patient department and antenatal care unit of General Hospital Idekpa, Benue state, Nigeria were offered PITC for HIV. The intervention was implemented by trained health professionals for the period spanning (June to December 2010). RESULTS: Among the 212 patients who were offered PITC for HIV, 199 (94%) accepted HIV testing, 10 patients (4.7%) opted out and 3 patients (1.4%) were undecided. Of the 199 participants who were tested for HIV, 9% were HIV seropositive. The PITC strategy was highly acceptable and feasible, and increased the number of patients who tested for HIV by 5% compared to voluntary counselling and testing. Findings from this assessment were consistent with those from other sub-Saharan African countries (such as Uganda and South Africa). CONCLUSION: PITC for HIV was highly acceptable and logistically feasible, and resulted in an increased rate of HIV testing among patients. Public health initiatives (such as the PITC strategy) that facilitate early detection of HIV and referral for early treatment should be encouraged for broader HIV control and prevention in Nigerian communities.

Human Immunodeficiency Virus and Risk of Type 2 Diabetes in a Large Adult Cohort in Jos, Nigeria.

BACKGROUND: Human immunodeficiency virus (HIV) infection and the use of antiretroviral therapy (ART) may increase the risk of type 2 diabetes mellitus (T2DM). However, data from regions with a high burden of HIV/AIDS are limited. We determined the prevalence of T2DM at the time of presentation to a large HIV clinic in Nigeria, as well as the incidence of diabetes 12 months following ART initiation. METHODS: Data from patients enrolled for ART from 2011 to 2013 was analyzed, including 2632 patients on enrollment and 2452 reevaluated after 12 months of ART commencement. The presence of diabetes, and demographic, clinical, and biochemical data were retrieved from standardized databases. CD4(+), HIV RNA load, and hepatitis C virus status were noted. Bivariate and logistic regressions were used to identify risk factors for T2DM. RESULTS: Baseline T2DM prevalence was 2.3% (95% confidence interval, 1.8%-2.9%); age, but not body mass index (BMI), was a risk factor for diabetes. After 12 months of ART, an additional 5.3% had developed T2DM. Newly developed diabetes was not associated with age, but was associated with BMI. There were no significant associations between prevalent or incident diabetes and CD4(+), viral load, or type of ART. CONCLUSIONS: Diabetes is not uncommon in HIV-infected individuals at the time of presentation to HIV services. Patients initiating ART have a high risk of developing diabetes in the first year of ART. Excessive weight gain should be avoided, as incident diabetes was associated with a BMI ≥25.0 kg/m(2).

Diarrhoea and Suboptimal Feeding Practices in Nigeria: Evidence from the National Household Surveys.

BACKGROUND: Globally, Nigeria has the largest burden of infectious diseases (including diarrhoea). Optimal feeding practices have been well-documented to protect against diarrhoea in other contexts; but this benefit has not been broadly studied in Nigeria. The study aimed to examine the association between diarrhoea and childhood feeding practices to provide country-specific evidence. METHOD: Data from the Nigeria Demographic and Health Survey for the period spanning 1999-2013 were used. Prevalence of diarrhoea by infant and young child feeding indicators was estimated, and the association between diarrhoea and childhood feeding indicators was examined using multilevel regression analyses. RESULTS: Prevalence of diarrhoea was higher among children whose mothers did not initiate breast feeding within the first hour of birth, infants who were not exclusively breastfed, and infants who were prematurely introduced to complementary foods. Early initiation of breast feeding was significantly associated with lower risk of diarrhoea (RR 0.68, 95% confidence interval (CI) 0.63, 0.74). Exclusively breastfed infants were less likely to develop diarrhoea compared to non-exclusively breastfed infants (RR 0.61, 95% CI 0.44, 0.86). Predominant breast feeding was significantly associated with a lower risk of diarrhoea (RR 0.66, 95% CI 0.54, 0.80). Bottle feeding and introduction of complementary foods were associated with a higher risk of diarrhoea. CONCLUSION: Early initiation of breast feeding as well as exclusive and predominant breast feeding protect against diarrhoea in Nigeria, while bottle feeding and introduction of complementary foods were risk factors for diarrhoea. Community- and facility-based initiatives are needed to improve feeding practices, and to reduce diarrhoea prevalence in Nigeria.

Transformation of HIV from pandemic to low-endemic levels: a public health approach to combination prevention.

Large declines in HIV incidence have been reported since 2001, and scientific advances in HIV prevention provide strong hope to reduce incidence further. Now is the time to replace the quest for so-called silver bullets with a public health approach to combination prevention that understands that risk is not evenly distributed and that effective interventions can vary by risk profile. Different countries have different microepidemics, with very different levels of transmission and risk groups, changing over time. Therefore, focus should be on high-transmission geographies, people at highest risk for HIV, and the package of interventions that are most likely to have the largest effect in each different microepidemic. Building on the backbone of behaviour change, condom use, and medical male circumcision, as well as expanded use of antiretroviral drugs for infected people and pre-exposure prophylaxis for uninfected people at high risk of infection, it is now possible to consider the prospect of what would be one of the most remarkable achievements in the history of public health: reduction of HIV transmission from a pandemic to low-level endemicity.

"Why should I take drugs for your infection?": outcomes of formative research on the use of HIV pre-exposure prophylaxis in Nigeria.

BACKGROUND: Nigeria has the second highest number of new HIV infections annually. Therefore, it is important to explore new strategies for preventing new infections. The introduction of pre-exposure prophylaxis (PrEP) for use by persons at high risk of HIV infection has new potential in preventing new HIV infections. The aim of this study is to explore the public opinion, community interest, and perceptions about the use and access to PrEP in Nigeria. METHODS: This formative study used a mixed method approach to collect data on public opinions and perceptions on appropriate target groups for PrEP access, community interest, perceptions about the use of PrEP as an HIV-prevention tool, how best to communicate with participants about PrEP, concerns about PrEP use by serodiscordant couples, and suggestions for the design and implementation of a PrEP demonstration project. Telephone and in-depth interviews were conducted, and focus group discussions and consultative meetings were held with critical stakeholders engaged in HIV-prevention, treatment, care, and support programmes in Nigeria. An online survey was also conducted. RESULTS: HIV serodiscordant couples were identified as the appropriate target group for PrEP use. Most respondents felt that PrEP use by key affected populations would help reduce the HIV incidence. Stigma was identified as a major concern and a potential barrier for the acceptance and use of PrEP by HIV serodiscordant couples. Electronic and print media were identified as important means for massive public education to prevent stigma and create awareness about PrEP. In a male dominated society such as Nigeria, HIV-negative male partners in serodiscordant relationships may resist enrolment in PrEP programmes. This may be complicated by the fact that the identified index partner in most serodiscordant relationships in Nigeria is an HIV-positive woman, who is often diagnosed during pregnancy. CONCLUSIONS: PrEP uptake and use by HIV serodiscordant couples in Nigeria may face notable but surmountable challenges. Much depends on the appropriateness of actions taken by multiple players. Motivation of HIV-negative male partners to use PrEP and establishment of effective public education programmes in addressing stigma are essential.

The use of antiretroviral therapy for the prevention of new HIV infection in populations at high risk for HIV sero-conversion in Nigeria.

The last few years have witnessed a renewed commitment to HIV prevention. The evidence to support the use of antiretroviral therapy (ART) for prevention of new HIV infection in the form of Pre-exposure prophylaxis (PrEP) among men who have sex with men, transgender, people who inject drugs, heterosexual men and women and HIV-1 serodiscordant couples, or treatment as prevention (TasP) for serodiscordant couples have also grown. The need to explore the possible use of ART for HIV prevention in Nigeria has become imperative in view of its high HIV burden and the current slow pace of effort to achieve the universal target of reducing its HIV incidence by 50%. While PrEP and TasP are welcome addendum to the existing HIV prevention armamentarium, it is still important to conduct a demonstration project to identify strategies that can facilitate access to PrEP and TasP taking cognizance of the peculiar local challenges with respect to ART and HIV prevention commodity access. The country has therefore drawn a roadmap for itself on how to introduce ART for use for HIV prevention as either PrEP or TasP. This paper discusses the three year national roadmap that would enable the country generated the needed scientific evidence as well as extensive community support for use of ART for HIV prevention in Nigeria. This process includes the conduct of modeling and formative studies, and the implementation of a 24 months demonstration project. The outcome of the demonstration project would inform plans for the scale up of pre-exposure prophylaxis (PrEP) access for population(s) at high risk for HIV infection in Nigeria.

Association of Bacterial vaginosis and other Sexually Transmitted Infections with HIV among pregnant women in Nigeria.

OBJECTIVES: To determine the association of Bacterial vaginosis (BV) and other sexually transmissible infections (STIs) with HIV prevalence among pregnant women in Jos, Nigeria. METHODS: This was a cross- sectional study of pregnant women who participated in the Prevention of Mother-to-Child Transmission of HIV program of the AIDS Prevention Initiative in Nigeria, between April 2002 and July 2004, at the Jos University Teaching Hospital in Jos, Nigeria. Blood, high vaginal and endocervical samples were obtained for diagnosis of HIV, BV and other STIs. Data were analyzed for prevalence of HIV, BV and other STIs. Univariate and multivariate logistic regression models generated unadjusted and adjusted odds ratios (OR) as well as 95% confidence intervals (CI) of the association of BV and other STIs with HIV prevalence. P value <0.05 was considered statistically significant. RESULTS: A total of 4,046 pregnant women were studied and 97.6% (3,950/4,046) had complete laboratory records for analysis. The prevalence of HIV was 8.2% (CI: 7.4-9.1); BV 11.9% (CI: 10.9-12.9); Candida 10.7% (CI: 9.7-11.7); mixed infection of BV and Candida 2.8% (CI: 2.3-3.4); Trichomonads 0.6% (CI: 0.3-0.8) and syphilis 0.35% (0.16-0.54). BV, Candida, mixed BV and Candida; and Trichomonads were independently associated with HIV infection [adjusted OR (95% CI), 2.9 (CI: 2.2-3.9); 2.0 (CI: 1.5-2.9); 3.4 (CI: 2.0-5.6), and 3.3 (CI: 1.1-9.7) respectively]. CONCLUSION: HIV prevalence is higher among pregnant women who have BV, Candida and Trichomonads vaginal infections compared with women who have no evidence of infection. The practice of routine screening for BV and other STIs among pregnant women as a strategy for identifying women at risk for prevalent HIV infection should be sustained/ encouraged and the syndromic management of STIs should be integrated into all antenatal care management protocols in antenatal clinics in order to curb the epidemic of heterosexual HIV transmission.

High-risk human papillomavirus among HIV-infected women with normal cervical cytology: a pilot study in Jos, Nigeria.

BACKGROUND: Cervical cancer is strongly linked to high-risk human papillomavirus (HR-HPV) and is typically preceded by cytological abnormalities. Less is known in patients with normal cervical cytology (NCC). We investigated the epidemiology of HR-HPV among HIV-infected women with NCC. METHODOLOGY: We conducted a cross-sectional study between January and June 2011 among HIV-infected women with NCC at an adult HIV clinic in Jos, Nigeria. Cervical sampling and analysis for HR-HPV by hybrid capture (HC2) with signal amplification was done to determine presence of one or more of the following HR-HPV types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 or 68. Epidemiologic factors associated with HR-HPV were determined using bivariate statistics and multivariate logistic regression. RESULTS: We evaluated 103 HIV-infected women with Pap cytology. The median age of the women was 32 years (range 21-49). Ninety-seven (94.2%) had NCC. Cervical samples for HR-HPV DNA testing were available from 89/97 (91.8%) of the HIV-infected women with NCC. Of the 89 women with cervical samples for HR-HPV DNA testing, 40 (44.9%) had detectable HR-HPV by HC2 giving a HR-HPV prevalence of 44.9% (95% CI 33.9-55.5%). Age < 30 years was associated with HR-HPV (OR 2.69 [95% CI 1.05-6.91, p = 0.039]) while history of previous abortion showed an inverse association with HR-HPV (OR 0.33[95% CI 0.15-0.94, p = 0.039]). CONCLUSION: The prevalence of HR-HPV is seemingly high among HIV-infected women with NCC in our clinical setting. These data provide support for further investigation of the clinical implications of positive HR-HPV among HIV-infected women with NCC report in cervical cancer prevention programs in Nigeria.

Fetal Health State Detection Using Interval Type-2 Fuzzy Neural Networks.

Diagnosis of fetal health is a difficult process that depends on various input factors. Depending on the values or the interval of values of these input symptoms, the detection of fetal health status is implemented. Sometimes it is difficult to determine the exact values of the intervals for diagnosing the diseases and there may always be disagreement between the expert doctors. As a result, the diagnosis of diseases is often carried out in uncertain conditions and can sometimes cause undesirable errors. Therefore, the vague nature of diseases and incomplete patient data can lead to uncertain decisions. One of the effective approaches to solve such kind of problem is the use of fuzzy logic in the construction of the diagnostic system. This paper proposes a type-2 fuzzy neural system (T2-FNN) for the detection of fetal health status. The structure and design algorithms of the T2-FNN system are presented. Cardiotocography, which provides information about the fetal heart rate and uterine contractions, is employed for monitoring fetal status. Using measured statistical data, the design of the system is implemented. Comparisons of various models are presented to prove the effectiveness of the proposed system. The system can be utilized in clinical information systems to obtain valuable information about fetal health status.

Prevalence of malaria parasitaemia in adult HIV-infected patients in Jos, North-central Nigeria.

BACKGROUND: Human immunodeficiency virus (HIV) and malaria co-infection has become an important public health problem in sub-Saharan Africa. Data on HIV and malaria interaction in Nigerian adults is scanty. We determined the prevalence of malaria parasitaemia in HIV-infected adults and further investigated the role of immune status in the HIV/malaria association. METHODS: This was a cross-sectional study involving 100 newly-diagnosed HIV-infected adults and 100 age and sex-matched HIV negative controls. Malaria parasitaemia was diagnosed by blood film microscopy using Giemsa staining technique and was defined as the presence of malaria parasites irrespective of species or parasite density. HIV infection was confirmed by western blot assay and CD4 T-lymphocyte count of the HIV-infected patients was quantified by flow cytometry. RESULTS: The prevalence of malaria parasitaemia was higher in HIV-infected adults (24%) than in the controls (9%) (chi2 = 8.17, p = 0.04). Participants residing in rural areas had higher prevalence of malaria parasitaemia than urban dwellers both for HIV-infected patients (34.1% Vs. 16.1%, chi2 = 4.3, p = 0.04) and controls (18.4%, Vs. 6.5%, chi2 = 3.4, p = 0.04). HIV-infected male patients tended to have malaria parasitemia more than their female counterparts (33.3% Vs. 17.2%, chi2 = 3.4, p = 0.06). Among HIV-infected patients, the prevalence of malaria parasitaemia progressively increased at lower CD4 cell counts, 10.3% for CD4 cell count of = 500, 17.5% for 200-499 and 45.2% for < 200 cells/microL (chi2 = 11.5, p = 0.003). CONCLUSION: HIV is likely to fuel malaria infection in tropical countries where both diseases are endemic. Malaria control practices should be further intensified in HIV-infected populations.

Effectiveness of three delivery models for promoting access to pre-exposure prophylaxis in HIV-1 serodiscordant couples in Nigeria.

OBJECTIVES: To evaluate the effectiveness of three models for pre-exposure prophylaxis (PrEP) service delivery to HIV-1 serodiscordant couples in Nigeria. METHODS: 297 heterosexual HIV-1 serodiscordant couples were recruited into three PrEP delivery models and followed up for 18 months. The models were i) Outpatient clinic model providing PreP in routine outpatient care; ii) Antiretroviral therapy (ART) clinic model providing PrEP in ART clinics; and iii) Decentralized care model providing PrEP through primary and secondary care centres linked to a tertiary care centre. The primary effectiveness endpoint was incident HIV-1 infection. The HIV incidence before and after the study was compared and the incidence rate ratio computed for each model. Survival analysis was conducted, Cox regression analysis was used to compare the factors that influenced couple retention in each of the models. Kaplan-Meier survival analysis was used to estimate the median retention time (in months) of the study participants in each of the study models, and log-rank test for equality of survival functions was conducted to test for significant differences among the three models. RESULTS: There was no significant difference (p>0.05) in the couple retention rates among the three models. At months 3, 6 and 9, adherence of the HIV-1-infected partners to ART was highest in the decentralized model, whereas at months 9 and 12, the outpatient model had the highest proportion of HIV-1- uninfected partners adhering to PrEP (p<0.001). The HIV incidence per 100 person-years was zero in the general outpatient clinic and ART clinic models and 1.6 (95% CI: 0.04-9.1) in the decentralized clinic model. The difference in the observed and expected incidence rate was 4.3 (95% CI: 0.44-39.57) for the decentralized clinic model. CONCLUSION: Although incidence of HIV seroconversion was highest in the decentralized clinic model, this difference may be due to the higher sexual risk behavior among study participants in the decentralized model rather than the type of service delivery. The study findings imply that any of the models can effectively deliver PrEP services.

Prognostic significance of BIRC7/Livin, Bcl-2, p53, Annexin V, PD-L1, DARC, MSH2 and PMS2 in colorectal cancer treated with FOLFOX chemotherapy with or without aspirin.

Evasion of apoptosis is associated with treatment resistance and metastasis in colorectal cancer (CRC). Various cellular processes are associated with evasion of apoptosis. These include overexpression of pro-apoptotic proteins (including p53 and PD-L1), anti-apoptotic proteins (BIRC7/Livin and Bcl-2), chemokine receptors (including DARC), and dysregulation of DNA mismatch repair proteins (including MSH2 and PMS2). The aim of this study was to determine the effect of folinic acid, 5-FU and oxaliplatin (FOLFOX) as a single agent and aspirin plus FOLFOX in various combinations on the aforementioned proteins in human CRC, SW480 cell line and rat models of N-Methyl-N-Nitrosourea (NMU)-induced CRC. In addition, effects of the NMU-induced CRC and chemotherapeutic regimens on haematological and biochemical parameters in the rat models were studied. Immunohistochemistry, immunofluorescence and immunoblot techniques were used to study the expression pattern of the related proteins in the human CRC cells pre- and post-treatment. Double contrast barium enema, post-mortem examination and histological analyses were used to confirm tumour growth and the effect of the treatment in vivo in rat models. Notably, we found in human mucinous CRC, a significant increase in expression of the BIRC7/Livin post-FOLFOX treatment compared with pre-treatment (p = 0.0001). This increase provides new insights into the prognostic role of BIRC7/Livin in evasion of apoptosis and facilitation of treatment resistance, local recurrence and metastasis particularly among mucinous CRCs post-FOLFOX chemotherapy. These poor prognostic features in the CRC may be further compounded by the significant suppression of DARC, PD-L1, PMS2 and overexpression of MSH2 and anti-apoptotic Bcl-2 and p53 proteins observed in our study (p < 0.05). Importantly, we found a significant reduction in expression of BIRC7/Livin and reactivation of DARC and PD-L1 with a surge in Annexin V expression in rat models of CRC cells post-treatment with a sequential dose of aspirin plus FOLFOX compared with other treatments in vivo (p <0.05). The mechanistic rational of these effects underscores the importance of expanded concept of possible aspirin combination therapy with FOLFOX sequentially in future CRC management. Validation of our findings through randomized clinical trials of aspirin plus FOLFOX sequentially in patients with CRC is therefore warranted.

Genetic diversity of Mycobacterium tuberculosis Complex in Jos, Nigeria.

BACKGROUND: Nigeria has a high tuberculosis incidence, and genotyping studies of Mycobacterium tuberculosis Complex (MTC) in the country are necessary in order to improve our understanding of the epidemic. METHODS: Isolates of MTC were isolated from cases of pulmonary tuberculosis in Jos, North Central region of Nigeria during 2006-2008. Drug susceptibility test (DST) was performed on 77 of 111 isolates by proportion method on Lowenstein Jensen (LJ) slope while genotyping of mycobacterial DNA was performed by spoligotyping. The SpolDB4 database and the model-based program 'spotclust' were used to assign isolates to families, subfamilies and variants. RESULTS: A total of 111 pulmonary isolates from consecutive tuberculosis patients in the city of Jos, Plateau State, Nigeria were spoligotyped. A total of 84 (76%) of the isolates belonged to the Latin American Mediterranean (LAM) family. Of these, 78 isolates were assigned to the LAM10 lineage. Among these, 66 exhibited identical spoligopatterns. Drug susceptibility profiles obtained were not consistently associated with any spoligopattern. CONCLUSIONS: The dominance of few M. tuberculosis lineages suggests either a high rate of transmission, frequent import of closely related strains, or a highly conserved genotype. It remains to be confirmed whether the predominance of identical LAM10 represent an outbreak.Spoligotyping was useful to gain an overall understanding of the local TB epidemic. This study demonstrated that the incidence of TB in Jos, Nigeria may be caused by a few successful M. tuberculosis families, dominated by the LAM10 family.

Patterns of Early-Onset Colorectal Cancer Among Nigerians and African Americans.

PURPOSE: Colorectal cancer (CRC) incidence rates are increasing among individuals < 50 years of age (early-onset CRC) globally with causes unknown. Racial/ethnic disparities in early-onset CRC have also grown more pronounced, because Black individuals have higher early-onset CRC incidence and poorer survival compared with White individuals. We describe the prevalence and burden of early-onset CRC among Africans in Nigeria and African Americans (AAs) in the United States. PATIENTS AND METHODS: We identified Black individuals diagnosed with a first primary CRC ages 18 to 49 years between 1989 and 2017 at Ahmadu Bello University Teaching Hospital in Zaria, Nigeria (Nigerians), and in the United States (AAs) using the National Institutes of Health/National Cancer Institute's SEER program of cancer registries. Multivariable logistic regression models were used to investigate clinical and demographic differences between Nigerians and AAs with early-onset CRC, adjusted for age, sex, tumor site, and histology. RESULTS: A total of 5,019 Black individuals were diagnosed with early-onset CRC over the study period (379 Nigerians; 4,640 AAs). Overall, approximately one third of young Black patients were diagnosed with rectal tumors (35.8%). Nigerian individuals with early-onset CRC were eight-fold more likely to be diagnosed with rectal tumors (odds ratio [OR], 8.14; 95% CI, 6.23 to 10.62; P < .0001) and more likely to be diagnosed at younger ages (OR, 0.87; 95% CI, 0.86 to 0.89; P < .0001) compared with young African Americans in adjusted models. CONCLUSION: Compared with AA individuals diagnosed with early-onset CRC, Nigerian individuals harbor distinct features of early-onset CRC. Additional investigation of the histopathologic and biologic heterogeneity of early-onset CRCs among Black individuals is critical for understanding racial disparities in susceptibility and outcomes, which may have implications for tailored early-onset CRC prevention, detection, and treatment strategies.