Epidemiology of Staphylococcus aureus carriage and disease among under five children in rural Gambia

Background: Data on the burden of severe Staphylococcus aureus disease, a significant cause of invasive bacterial infections among children aged <5 years in The Gambia and Africa at large, are lacking. The work in this thesis estimates the burden (cases and deaths) of severe S. aureus disease in Africa, the incidence of S. aureus bacteraemia (SAB) in children aged <5 years and assesses the risk factors for neonatal S. aureus acquisition in rural Gambia. Methods: This thesis includes three separate studies. First, following a systematic literature review and meta-analysis, raw and processed data were synthesised to estimate the numbers of cases and deaths due to severe S. aureus diseases in children aged <5 years in Africa. Second, the incidence and case fatality ratio (CFR) of SAB in <5 years Gambian children were estimated from a population-based study. Lastly, a longitudinal study of newborn-contact pairs was used to evaluate the risk factors associated with neonatal S. aureus carriage at birth as well as with its acquisition at one-week of age. Results: In Africa, an estimated 392,066 cases and 46,467 deaths due to severe S. aureus disease occurred among children aged <5 years with 20.4% and 58.4% of these occurring among neonates, respectively in 2015. The incidence of SAB among Gambian children aged <5 years and neonates was 78/100,000 person-years (95%CI 67–91) and 3.5/1,000 live-births (95%CI 2.9–4.7), respectively. The CFR was 14.1% (95%CI 9.6-19.8). S. aureus carriage at birth was associated with the midwife’s report of handwashing before delivery while carriage acquisition one week after delivery was associated with maternal and household child nasal carriage. Conclusion: The burden of severe S. aureus disease among children aged <5 years in Africa is substantial. Developing new, and implementing existing, strategies urgently to tackle this will contribute to achieving the sustainable development goals

Pregnancy and contraceptive use among women participating in an HIV prevention trial in Tanzania.

OBJECTIVES: Information on pregnancy rates and factors associated with pregnancy and contraceptive use is important for clinical trials in women in sub-Saharan Africa where withdrawal of investigational products may be required in the event of pregnancy with a consequent effect on sample size and trial power. METHODS: A prospective cohort analysis of pregnancy and contraceptive use was conducted in Tanzanian women enrolled in a randomised placebo-controlled trial of herpes simplex virus-suppressive therapy with acyclovir to measure the effect on HIV incidence in HIV-negative women and on genital and plasma HIV viral load in HIV-positive women. The cohort was followed every 3 months for 12-30 months. Women at each visit were categorised into users or non-users of contraception. Pregnancy rates and factors associated with pregnancy incidence and contraceptive use were measured. RESULTS: Overall 254 of 1305 enrolled women became pregnant at least once during follow-up (pregnancy rate: 12.0/100 person-years). Younger age, being unmarried, higher baseline parity and changes in contraceptive method during follow-up were independently associated with pregnancy. Having paid sex and being HIV positive were associated with lower risk of pregnancy. Uptake of contraception was associated with young age, being unmarried, occupation, parity and the number and type of sexual partners. CONCLUSIONS: Data on use of contraceptive methods and risk factors for pregnancy can help to guide decisions on trial eligibility and the need for additional counselling. Mandatory reliable contraceptive use in study participants may be required to reduce pregnancy rates in studies where pregnancy is contraindicated

Fruits and Vegetables Diet Improves Kidney Functions and Electrolyte Status in Non-Insulin Dependent Diabetes Mellitus (N.I.D.D.M) Subjects

Kidney failure and electrolyte imbalance are some of the complications associated with diabetes mellitus, if prompt treatment is not instituted it may lead to renal disease and dietary influence has been established on the prognosis of many diseases. Thus effects of fruits and vegetables diet were investigated on kidney functions and electrolyte status of some selected Non-Insulin dependent diabetic subjects at the cardiovascular clinic of Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria. The patients with mean fasting blood glucose (FBG) 7.84± 0.95 mmol dl-1 were placed on 300 g of fruits and vegetables per day in addition to their normal drugs and food intake for eight weeks. Standard laboratory methods were employed for biochemical assay; while the data were analyzed using analytic and descriptive statistics. A significant difference (p &lt; 0.05) was noticed between baseline and eighth week’s values in the following parameters: plasma creatinine, 3.48± 0.095 to 1.79±0.57 mgdL-1; urea, 39.05±2.04-23.20±1.50 and uric acid 5.37± 0.27-2.50±0.59 mgdL-1. No significant difference (p &gt; 0.05) was observed in plasma electrolyte values when the    baseline value were compared with the eighth week’s values. After the eight weeks, the fruits and vegetables rations were stopped for two weeks and the parameters were measured again. Significant difference(p&lt;0.05) were observed in all the values by comparing week eight with week ten values; plasma creatinine, 1.79±0.52 to 3.01± 0.68 mgdl-1,plasma urea, 39.05± 2.40 to 23.20± 1.50  mgdl-1 and plasma uric acid 2.50±0.59 to 3.61±0.50 mgd-1, however no significant difference (p&gt; 0.05) was observed in serum electrolyte. Our results showed that fruits and vegetables consumption improved kidney function and did not affect plasma electrolytes adversely. KEY WORDS: Diabetes mellitus, kidney functions, creatinine, urea, uric acid fruits and vegetable

Prolonged operative time increases risk of blood loss and transfusion requirements in revision hip surgery.

INTRODUCTION: Revision hip surgery is well documented to have a high association with substantial blood loss and the associated need for a blood transfusion. This exposes the patient to increased risk of transfusion reaction and blood borne infection. There are many strategies to minimize allogeneic transfusion rates in revision surgery such as pre-operative autologous donation, peri-operative tranexamic acid, thrombin sealants, normovolaemic haemodilution, intra-operative blood salvage and the use of post-operative autologous drains. PATIENTS AND METHODS: We prospectively looked at 177 consecutive cases performed at one centre by a single surgical and anaesthetic team to identify which patient and operative factors were most significant in minimizing the requirement for an allogeneic blood transfusion. RESULTS: Our results identified the duration of surgery as being the only significant variable affecting the level of blood loss. We noted a 3% increase in the probability of massive blood loss (> 2000 mls) for every minute of increased surgical time in our series. CONCLUSIONS: We conclude that measures to minimize the duration of surgery would be beneficial in reducing blood loss and the risks of requiring blood transfusions in revision hip surgery

Test-Retest Reliability of Self-Reported Sexual Behavior History in Urbanized Nigerian Women.

BACKGROUND: Studies assessing risk of sexual behavior and disease are often plagued by questions about the reliability of self-reported sexual behavior. In this study, we evaluated the reliability of self-reported sexual history among urbanized women in a prospective study of cervical HPV infections in Nigeria. METHODS: We examined test-retest reliability of sexual practices using questionnaires administered at study entry and at follow-up visits. We used the root mean squared approach to calculate within-person coefficient of variation (CVw) and calculated the intra-class correlation coefficient (ICC) using two way, mixed effects models for continuous variables and [Formula: see text] statistics for discrete variables. To evaluate the potential predictors of reliability, we used linear regression and log binomial regression models for the continuous and categorical variables, respectively. RESULTS: We found that self-reported sexual history was generally reliable, with overall ICC ranging from 0.7 to 0.9; however, the reliability varied by nature of sexual behavior evaluated. Frequency reports of non-vaginal sex (agreement = 63.9%, 95% CI: 47.5-77.6%) were more reliable than those of vaginal sex (agreement = 59.1%, 95% CI: 55.2-62.8%). Reports of time-invariant behaviors were also more reliable than frequency reports. The CVw for age at sexual debut was 10.7 (95% CI: 10.6-10.7) compared with the CVw for lifetime number of vaginal sex partners, which was 35.2 (95% CI: 35.1-35.3). The test-retest interval was an important predictor of reliability of responses, with longer intervals resulting in increased inconsistency (average change in unreliability for each 1 month increase = 0.04, 95% CI = 0.07-0.38, p = 0.005). CONCLUSION: Our findings suggest that overall, the self-reported sexual history among urbanized Nigeran women is reliable

Reactogenicity, safety and immunogenicity of a protein-based pneumococcal vaccine in Gambian children aged 2-4 years: A phase II randomized study.

Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2-4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2-4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic

Kinetics of antibodies against pneumococcal proteins and their relationship to nasopharyngeal carriage in the first two months of life.

INTRODUCTION: The currently used Streptococcus pneumoniae vaccines have had a significant impact on the pneumococcal diseases caused by the serotypes they cover. Their limitations have stimulated a search for alternate vaccines that will cover all serotypes, be affordable and effective in young children. Pneumococcal protein antigens are potential vaccine candidates that may meet some of the shortfalls of the current vaccines. Thus, this study aimed to determine the relationship between antibodies against pneumococcal protein antigens and nasopharyngeal carriage in infants. METHODS: One hundred and twenty mother-infant pairs were enrolled into the study. They had nasopharyngeal swabs(NPS) taken at birth and every two weeks for the first eight weeks after delivery, and blood samples were obtained at birth and every four weeks for the first eight weeks after delivery. Nasopharyngeal carriage of S. pneumoniae was determined from the NPS and antibodies against the pneumococcal proteins CbpA, PspA and rPly were measured in the blood samples. RESULTS: The S. pneumoniae carriage rate in infants increased to that of mothers by eight weeks of age. The odds of carriage in infants was 6.2 times (95% CI: 2.0-18.9) higher when their mothers were also carriers. Bacterial density in infants was lower at birth compared to their mothers (p = 0.004), but increased with age and became higher than that of their mothers at weeks 4 (p = 0.009), 6 (p = 0.002) and 8 (p<0.0001). At birth, the infants' antibodies against CbpA, and rPly pneumococcal protein antigens were similar, but that of PspA was lower (p<0.0001), compared to their mothers. Higher antibody concentrations to CbpA [OR (95% CI): 0.49 (0.26-0.92, p = 0.03)], but not PspA and rPly, were associated with protection against carriage in the infants. CONCLUSION: Naturally induced antibodies against the three pneumococcal protein antigens were transferred from mother to child. The proportion of infants with nasopharyngeal carriage and the bacterial density of S. pneumoniae increased with age within the first eight weeks of life. Higher concentrations of antibodies against CbpA, but not PspA and rPly, were associated with reduced risk of nasopharyngeal carriage of S. pneumoniae in infants

Recurrence of cervical intraepithelial lesions after thermo-coagulation in HIV-positive and HIV-negative Nigerian women

Background: The burden of cervical cancer remains huge globally, more so in sub-Saharan Africa. Effectiveness of screening, rates of recurrence following treatment and factors driving these in Africans have not been sufficiently studied. The purpose of this study therefore was to investigate factors associated with recurrence of cervical intraepithelial lesions following thermo-coagulation in HIV-positive and HIV-negative Nigerian women using Visual Inspection with Acetic Acid (VIA) or Lugol’s Iodine (VILI) for diagnosis. Methods: A retrospective cohort study was conducted, recruiting participants from the cervical cancer “see and treat” program of IHVN. Data from 6 sites collected over a 4-year period was used. Inclusion criteria were: age ≥18 years, baseline HIV status known, VIA or VILI positive and thermo-coagulation done. Logistic regression was performed to examine the proportion of women with recurrence and to examine factors associated with recurrence. Results: Out of 177 women included in study, 67.8 % (120/177) were HIV-positive and 32.2 % (57/177) were HIV-negative. Recurrence occurred in 16.4 % (29/177) of participants; this was 18.3 % (22/120) in HIV-positive women compared to 12.3 % (7/57) in HIV-negative women but this difference was not statistically significant (p-value 0.31). Women aged ≥30 years were much less likely to develop recurrence, adjusted OR = 0.34 (95 % CI = 0.13, 0.92). Among HIV-positive women, CD4 count <200cells/mm3 was associated with recurrence, adjusted OR = 5.47 (95 % CI = 1.24, 24.18). Conclusion: Recurrence of VIA or VILI positive lesions after thermo-coagulation occurs in a significant proportion of women. HIV-positive women with low CD4 counts are at increased risk of recurrent lesions and may be related to immunosuppression

Tuning the Sensitivity of an Optical Cavity with Slow and Fast Light

We have measured mode pushing by the dispersion of a rubidium vapor in a Fabry-Perot cavity and have shown that the scale factor and sensitivity of a passive cavity can be strongly enhanced by the presence of such an anomalous dispersion medium. The enhancement is the result of the atom-cavity coupling, which provides a positive feedback to the cavity response. The cavity sensitivity can also be controlled and tuned through a pole by a second, optical pumping, beam applied transverse to the cavity. Alternatively, the sensitivity can be controlled by the introduction of a second counter-propagating input beam that interferes with the first beam, coherently increasing the cavity absorptance. We show that the pole in the sensitivity occurs when the sum of the effective group index and an additional cavity delay factor that accounts for mode reshaping goes to zero, and is an example of an exceptional point, commonly associated with coupled non-Hermitian Hamiltonian systems. Additionally we show that a normal dispersion feature can decrease the cavity scale factor and can be generated through velocity selective optical pumpin