Biobele J. Brown

Disclosure of HIV status to infected children in a Nigerian HIV Care Programme

With increasing survival of HIV-infected children, parents face the challenges of disclosure to the children. The aim of this study was to assess the rate of HIV disclosure to children in Ibadan and the factors influencing it in order to guide design of strategies for successful disclosure. A semi-structured questionnaire was administered to consecutive consenting caregivers of HIV-infected children aged ≥6 years attending the Paediatric Infectious Disease Clinic of the University College Hospital, Ibadan, between November 2008 and October 2009. Caregivers of 96 children (46 boys, 50 girls) infected with HIV were interviewed. The ages of the children ranged from 6 to 14 years with a mean (SD) of 8.8 (2.2) years. Disclosure had been done in only 13 (13.5%) of the children; ages at disclosure ranged from 4.5 to 13 years with a mean of 8.7 (SD = 2.2). Disclosure was associated with age above 10 years. Reasons given by carers for non-disclosure in 83 caregivers included inability of the children to understand in 53 (63.9%), fear of disclosure to other children 34 (41.0%), fear of disclosure to family/friends in 28 (33.7%), fear of psychological disturbance of the children in 26 (31.3%) and fear of blaming the parents in 22 (26.5%). Twenty (20.8%) of the children have asked questions relating to their diagnosis and the responses are often evasive. Caregivers felt disclosure had helped adherence to antiretroviral therapy in 7 (63.6%) of the 11 children on antiretroviral drugs in whom there was disclosure but no effect on the remaining. There is a need to assist parents and health care providers in successfully disclosing HIV status to infected children without adverse consequences.

Current sickle cell disease management practices in Nigeria

BACKGROUND Although Nigeria has the highest burden of sickle cell disease (SCD) worldwide, there is still variable and poor utilisation of standard-of-care practices for SCD patients in the country. METHODS This was a questionnaire survey of doctors in some dedicated SCD clinics in Nigeria in order to document the facilities available and common management practices. RESULTS There were responses from 18 clinics based in 11 institutions. The number of patients being followed in each centre ranged from 15 to approximately 11 000. All clinics provided malaria prophylaxis and folic acid routinely to their patients. Only eight clinics prescribe penicillin prophylaxis. Eight prescribe hydroxyurea to patients who can afford it when indicated. All of the centres except three have electronic cell counters, but all had access to haemoglobin electrophoresis. Three had high-performance liquid chromatography machines installed but none was being routinely used. One institution had a functioning molecular biology laboratory. There is no official newborn screening programme in the country. All had access to microbiology and chemistry laboratories. Nine institutions had CT, six had MRI and three had transcranial Doppler facilities. CONCLUSION The care available for SCD in Nigeria is still suboptimal and there is an urgent need for concerted effort to tackle the problem, but to make a significant impact on the burden of the disease would require more focus at the primary care level. Some steps to achieving this are outlined.

Circulatory hepcidin is associated with the anti-inflammatory response but not with iron or anemic status in childhood malaria

Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore, it is important to understand the pathology underlying the development of CM and SMA as opposed to uncomplicated malaria (UM). Increased levels of hepcidin have been associated with UM, but its level and role in severe malarial disease remains to be investigated. Plasma and clinical data were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, Nigeria. Here, we report that hepcidin levels are lower in children with SMA or CM than in those with milder outcome (UM). While different profiles of pro- and anti-inflammatory cytokines were observed between the malaria syndromes, circulatory hepcidin levels remained associated with the levels of its regulatory cytokine interleukin-6 and of the anti-inflammatory cytokine inerleukin-10, irrespective of iron status, anemic status, and general acute-phase response. We propose a role for hepcidin in anti-inflammatory processes in childhood malaria.

Infant-feeding pattern of HIV-positive women in a prevention of mother-to-child transmission (PMTCT) programme.

Abstract Objectives. To evaluate the infant-feeding choices, practices and possible determinants among HIV-positive women enrolled in a prevention of mother-to-child transmission programme in Ibadan, Nigeria. Methods. A cross-sectional survey involving HIV-positive women who had received infant-feeding counselling prior to delivery. A structured questionnaire was administered at ≤ 72 hrs and not ≥ 6 weeks of delivery and was complemented with an in-depth interview. Results. A total of 241 women were studied. The choice of infant feeding was formula for 223 (93.5%) and in actual practice, 9 (3.7%) mothers admitted mixed feeding. There was no statistical significant difference between the feeding pattern and the socio-demographic characteristics. The major factor influencing the choice of infant feeding was “The desire to reduce the risk of transmission” which was recorded among 204 (84.6%) of the women. Greatest support in maintaining infant-feeding option was the spouse (36.1%). From the in-depth interview of 23 non-breastfeeding (infant formula) mothers, the major challenge faced was stigmatisation. Conclusion. Despite the premium placed on breastfeeding in this locality, with infant-feeding counselling, most HIV-positive women chose and practiced formula feeding. It is necessary to address how best HIV-positive mothers could handle or overcome criticisms and stigmatisation by others.

Affinity Proteomics Reveals Elevated Muscle Proteins in Plasma of Children with Cerebral Malaria

Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria.

Hydroxyurea lowers transcranial Doppler flow velocities in children with sickle cell anaemia in a Nigerian cohort

Background Sickle cell anaemia (SCA) is the leading genetic disorder in Nigeria. Elevated velocities ≥170 cm/sec occur in about a third of Nigerian children with SCA. Chronic blood transfusion for stroke prevention is faced with a myriad of challenges in our practice. Objectives To evaluate the effectiveness of hydroxyurea (HU) in reducing flow velocities in a cohort of Nigerian children with SCA and elevated velocities treated with HU. Methods An observational study was carried out on a cohort of Nigerian children with SCA and elevated velocities identified on routine transcranial Doppler (TCD) screening. HU was recommended in those with TCD velocities ≥ 170cm/sec as stipulated in our hospital protocol. Outcomes were compared after ≥12 months of observation. Results Fifty children with elevated TCD velocities were studied; 31 consented to HU therapy and 19 declined. Children on HU showed a statistically significant decline in mean velocities from 199.7 [17.1] cm/sec to 165.8 [20.7] cm/sec (P < 0.001) with a significant increase in mean packed cell volume from 21.1 [3.4] to 25.0 [2.8]%. Children without treatment had a significant rise in mean velocities from 190.2 [10.8] cm/sec to 199.7 [14.9] cm/sec (P = 0.003). Children with conditional risk velocities on HU were less likely to convert to abnormal risk (P < 0.001). Two stroke events occurred, one in each group. No adverse effects of HU were recorded in the cohort. Conclusion HU appears to significantly reduce TCD velocities in Nigerian children with SCA and elevated velocities ≥170 cm/sec with beneficial effect on the haematological profile. HU may provide an effective approach to primary stroke prevention, particularly in Africa. Pediatr Blood Cancer 2015;62:1587–1591.

Treatment of Burkitt lymphoma in equatorial Africa using a simple three-drug combination followed by a salvage regimen for patients with persistent or recurrent disease

Prior to the introduction of the International Network for Cancer Treatment and Research (INCTR) protocol INCTR 03‐06, survival of patients with Burkitt lymphoma at four tertiary care centres in equatorial Africa was probably no more than 10–20%. The results reported here for 356 patients have demonstrated marked improvement in survival through the use of a uniform treatment protocol consisting of cyclophosphamide, methotrexate, vincristine, and intrathecal therapy, and the introduction of non‐cross resistant second‐line (salvage) therapy, consisting of ifosfamide, mesna, etoposide and cytarabine, when patients failed to achieve a complete response to first‐line therapy or relapsed early. Overall survival rates of 67% and 62% were observed at 1 and 2 years (relapse is rare after 1 year of remission). Of interest was the small impact of cerebrospinal fluid (CSF) and bone marrow involvement on outcome. However, the presence or absence of abdominal involvement clearly defined two prognostic groups. An additional finding was the association between CSF pleocytosis and orbital tumours, suggesting that spread of tumour cells to the central nervous system may sometimes occur via direct involvement of cranial nerves in the orbit. Survival rates may be increased in patients with abdominal involvement by combining first‐ and second‐line therapy, but verification will require a further clinical study.

Prevalence and clinical pattern of paediatric HIV infection at the University College Hospital, Ibadan, Nigeria: a prospective cross-sectional study

BackgroundThe prevalence of Paediatric HIV infection is largely unknown in many countries in sub-Saharan Africa. This study was aimed at determining the prevalence, clinical pattern of HIV infection and outcome among new patients aged <15 years using age-specific diagnostic methods.MethodsA prospective cross sectional study was carried out using the provider initiated HIV testing and counselling (PITC) model. HIV rapid test in parallel was used for screening and confirmation was with HIV DNA PCR in children <18 months and Western Blot in children ≥ 18 months.ResultsA total of 600 children were enrolled with ages ranging between one day and 179 months. Male: female ratio was 1.2:1. HIV seroprevalence was 12.3% and after confirmatory tests, the prevalence was 10%. Fourteen (37.8%) of the children aged less 18 months were exposed but not infected. Mother-to-child transmission accounted for 93.3% of cases. Features predictive of HIV infection were diarrhoea, cough, weight loss, ear discharge generalized lymphadenopathy, presence of skin lesions, parotid swelling and oral thrush. About 75% presented in advanced or severe clinical stages of the disease, 56.8% had severe immunodeficiency while 50% had viral loads more than 100,000 copies/ml. Mortality rate was 14.3% among HIV positive compared with 11.3% in HIV negative children but was not significant. Among the HIV positive children, 26.7% were orphans.ConclusionsThe prevalence rate of HIV infection among new patients screened using the PITC model was high, majority resulting from mother-to-child transmission. Most children presented in advanced stages of the disease and mortality rate among them was high. Though, the study site being a referral centre might have contributed to the high prevalence observed in this study, there is a need to expand access to PMTCT services, ensure implementation of PITC in paediatric settings and expand support services for HIV infected children.

Malaria Induces Anemia through CD8 + T Cell-Dependent Parasite Clearance and Erythrocyte Removal in the Spleen

ABSTRACT  Severe malarial anemia (SMA) in semi-immune individuals eliminates both infected and uninfected erythrocytes and is a frequent fatal complication. It is proportional not to circulating parasitemia but total parasite mass (sequestered) in the organs. Thus, immune responses that clear parasites in organs may trigger changes leading to anemia. Here, we use an outbred-rat model where increasing parasite removal in the spleen escalated uninfected-erythrocyte removal. Splenic parasite clearance was associated with activated CD8+ T cells, immunodepletion of which prevented parasite clearance. CD8+ T cell repletion and concomitant reduction of the parasite load was associated with exacerbated (40 to 60%) hemoglobin loss and changes in properties of uninfected erythrocytes. Together, these data suggest that CD8+ T cell-dependent parasite clearance causes erythrocyte removal in the spleen and thus anemia. In children infected with the human malaria parasite Plasmodium falciparum, elevation of parasite biomass (not the number of circulating parasites) increased the odds ratio for SMA by 3.5-fold (95% confidence intervals [CI95%], 1.8- to 7.5-fold). CD8+ T cell expansion/activation independently increased the odds ratio by 2.4-fold (CI95%, 1.0- to 5.7-fold). Concomitant increases in both conferred a 7-fold (CI95%, 1.9- to 27.4-fold)-greater risk for SMA. Together, these data suggest that CD8+-dependent parasite clearance may predispose individuals to uninfected-erythrocyte loss and SMA, thus informing severe disease diagnosis and strategies for vaccine development. IMPORTANCE Malaria is a major global health problem. Severe malaria anemia (SMA) is a complex disease associated with partial immunity. Rapid hemoglobin reductions of 20 to 50% are commonly observed and must be rescued by transfusion (which can carry a risk of HIV acquisition). The causes and risk factors of SMA remain poorly understood. Recent studies suggest that SMA is linked to parasite biomass sequestered in organs. This led us to investigate whether immune mechanisms that clear parasites in organs trigger anemia. In rats, erythropoiesis is largely restricted to the bone marrow, and critical aspects of the spleen expected to be important in anemia are similar to those in humans. Therefore, using a rat model, we show that severe anemia is caused through CD8+ T cell-dependent parasite clearance and erythrocyte removal in the spleen. CD8 activation may also be a new risk factor for SMA in African children. Malaria is a major global health problem. Severe malaria anemia (SMA) is a complex disease associated with partial immunity. Rapid hemoglobin reductions of 20 to 50% are commonly observed and must be rescued by transfusion (which can carry a risk of HIV acquisition). The causes and risk factors of SMA remain poorly understood. Recent studies suggest that SMA is linked to parasite biomass sequestered in organs. This led us to investigate whether immune mechanisms that clear parasites in organs trigger anemia. In rats, erythropoiesis is largely restricted to the bone marrow, and critical aspects of the spleen expected to be important in anemia are similar to those in humans. Therefore, using a rat model, we show that severe anemia is caused through CD8+ T cell-dependent parasite clearance and erythrocyte removal in the spleen. CD8 activation may also be a new risk factor for SMA in African children.

Chronic blood transfusion for primary and secondary stroke prevention in Nigerian children with sickle cell disease: A 5‐year appraisal

Chronic blood transfusion (CBT) diminishes the risk of primary and secondary stroke in sickle cell disease (SCD). We appraised CBT and assessed its feasibility as an option for stroke prevention in a setting of limited resources.Background Chronic blood transfusion (CBT) diminishes the risk of primary and secondary stroke in sickle cell disease (SCD). We appraised CBT and assessed its feasibility as an option for stroke prevention in a setting of limited resources. Methods All new cases of SCD seen in the Paediatric Hematology/Neurology units of the University College Hospital, Ibadan, Nigeria over a 5-year period were screened and followed up to identify those who had an indication for CBT for stroke prevention. Caregivers were counseled and offered CBT when indicated. Children of caregivers who accepted chronic transfusion were carefully followed up and outcomes documented. Results Five (10%) of the caregivers of the 50 children who had an indication for CBT for stroke prevention consented to the treatment. They all had homozygous sickle cell anemia and had suffered a stroke. None of the children with abnormal TCD velocities consented to CBT. Two children experienced transfusion reactions, fatal in one. The mean annual cost of chronic transfusion (without chelation) was