Data on childhood cancers in Africa are sparse, particularly since the spread of HIV. We aimed to... more Data on childhood cancers in Africa are sparse, particularly since the spread of HIV. We aimed to document the frequency of pediatric cancers presenting to a large central hospital in Malawi, detailing the presenting features, initial investigations, and HIV status of these children. A retrospective audit of the spectrum and clinical presentation of cancers among children (<16 years) seen at Queen Elizabeth's Central Hospital (QECH), between 1998 and 2003. Seven hundred seven children with cancer were seen, the number of cases per year increased over the time period; 50% (351) had Burkitt lymphoma, 13% (89) had retinoblastoma, and 9% (61) had Kaposi sarcoma, with a variety of other tumors comprising the remainder. Kaposi sarcoma markedly increased in frequency over time. Histological verification of diagnosis was available for 49% (348). The proportion of children with cancer who were tested for HIV increased over time, but varied by cancer type. Amongst those tested, the seroprevalence was 93% (52/56) for children with Kaposi sarcoma, 4% (11/289) for those with Burkitt lymphoma, 31% (8/26) for those with other non-Hodgkin lymphomas, 7% (1/15) for those with Hodgkin disease, and 5% (5/103) for those with other cancers. The number of cases seen per year has increased over the study period for almost all cancers, but in particular for Kaposi sarcoma. Burkitt lymphoma remains the commonest pediatric tumor in Malawi. In the case of Burkitt lymphoma, non-Hodgkin lymphoma, and Kaposi sarcoma there is a significant difference in the presentation of HIV-seropositive and -seronegative children.
Journal of health, population, and nutrition, 2005
This prospective study was carried out during February 2000-April 2003 to characterize the relati... more This prospective study was carried out during February 2000-April 2003 to characterize the relationship between the status of carotenoids, vitamin E, and retinol and anthropometric status in apparently healthy infants and their mothers in Blantyre, Malawi. Anthropometric status of infants and concentrations of carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene), retinol, and alpha-tocopherol in plasma were measured in 173 infants at 12 months of age, and concentrations of carotenoids, retinol, and a-tocopherol in plasma were measured in their mothers two weeks postpartum. In multivariate analyses, concentrations of retinol, total carotenoids, non-provitamin A carotenoids, and alpha-tocopherol in infants were associated with under-weight (p = 0.05). Concentrations of a-tocopherol were associated with wasting (p = 0.04). Concentrations in mothers and infants were all correlated (correlation coefficients from 0.230 to 0.502, p < 0.003). ...
We previously reported 57% 12-month event free survival (EFS) in Malawian children with stage I t... more We previously reported 57% 12-month event free survival (EFS) in Malawian children with stage I to III Burkitt lymphoma (BL) with an intermediate dose chemotherapy protocol lasting 77 days. This protocol was shortened to 42 days and evaluated in children with stage I to IV disease for EFS and toxicity. All Malawian children admitted to Queen Elizabeth Central Hospital, from 03/08/2000 to 12/03/2002 with confirmed BL were eligible. A fine needle aspirate, bone marrow aspirate, cerebrospinal fluid cytology, haemoglobin (Hb), white cell count (WCC), malaria smear, ELISA for HIV, and abdominal ultrasound were performed routinely. Murphy staging was used. The first dose of chemotherapy (COP1) consisted of 300 mg cyclophosphamide (CPM), 1 mg vincristine, and 60 mg prednisone given on day 1 and followed by COP2 on day 8 (only for patients with larger tumour volumes, stage III or IV disease). The vincristine dose in COP2 was 2 mg. COMP1 and 2 given on days 22 and 36 consisted of 500 mg CPM, 2 mg vincristine, 60 mg prednisone, and 2 g methotrexate. All doses were calculated per body surface area. Intrathecal methotrexate and hydrocortisone were given with COP1 and 2. Forty-two patients, 30 boys and 12 girls median ages 6 and 7.5 years, respectively, had Murphy stage I(n5), II(n8), III(n21), and IV(n8) disease. The face was involved in 74%, abdomen in 55%, bone marrow in 14%, kidneys in 24%, and 12% had paraplegia. Fourteen children died during or shortly after completion of chemotherapy. Three of these were disease related. Twelve patients suffered a local relapse after 57-328 days, and one a CNS relapse at 76 days. The projected EFS at 12 months is 50% in stage I, 50% in stage II, 24% in stage III, 25% in stage IV, and 33% for all patients. The cumulative mean dose of CPM was 62 mg/kg in survivors and 64 mg/kg in children who relapsed. One third of patients experienced significant marrow suppression, and infections after COMP1. Thirty-three percent of children are in first remission at 12 months. The morbidity and mortality of treatment was high. The high relapse rate in all stages may be due to the low cumulative dose of CPM.
Interferons (IFNs) associated with pregnancy were studied for their possible role in inhibition o... more Interferons (IFNs) associated with pregnancy were studied for their possible role in inhibition of vertical transmission of the human immunodeficiency virus type 1 (HIV-1). A study group was composed of 43 HIV-1-positive mothers, of whom 15 transmitted the virus to the offspring and 28 did not. The control group included 48 HIV-1-negative mother-infant pairs. The IFN-alpha was detected only sporadically in the maternal sera from the groups of transmitters (27%), nontransmitters (21%), and controls (19%). The average levels of IFN-alpha were low, 16.3 +/- 2.5 pg/ml, 21.4 +/- 9.9 pg/ml, and 21.3 +/- 9.4 pg/ml among the transmitters, nontransmitters, and control subjects, respectively. In the cord blood, IFN-alpha was detected only on two occasions among transmitters, and on a single occasion in the control group. IFN-beta was absent from both maternal and cord blood in the study group, and found to be present in one case in the control group simultaneously in the maternal and fetal sera. In the placentas, on the other hand, both type I and II IFNs were expressed universally in the villous trophoblast, and IFN-alpha and -beta in the stromal macrophages as well. In one case among transmitters, no IFNs were detected; nevertheless, no significant difference with respect to nontransmitters could be confirmed. Our data suggest that although the placental IFNs have an antiviral potential, they are not sufficient to suppress transmission of HIV from mother to infant.
to describe the seroprevalence of hepatitis B (HBV) and C (HCV) infection in HIV-positive and HIV... more to describe the seroprevalence of hepatitis B (HBV) and C (HCV) infection in HIV-positive and HIV-negative pregnant women from rural Malawi. descriptive study using serum samples collected between 1993-1995 in the Shire valley in rural Malawi. Fifty HIV-positive and 100 HIV-negative samples were selected randomly from 153 HIV-positive and 443 HIV-negative women delivering in the hospital. evidence of HBV and HCV infection was found in 71.7 and 16.5% of women, respectively. Chronic carriage of HBV (HBsAg positive) is high (13%) and in agreement with prevalences reported from highly endemic areas. Exposure to HBV and HCV probably occurred well before adulthood as the prevalence of anti-HBc antibody was high in young mothers &amp;amp;lt;20 years of age (22/27; 81%). HBV and HCV infections are highly endemic in rural Malawi. There was no statistical evidence to suggest that HIV positivity was associated with an increased prevalence of HBV or HCV markers. Infection with HBV or HCV was not statistically associated.
To measure hepatic and hematological parameters among neonates randomized to receive ultra-short ... more To measure hepatic and hematological parameters among neonates randomized to receive ultra-short antiretroviral regimens. As part of an on-going clinical trial in Malawi, infants born to women who received (early presenters) or did not receive (late presenters) standard intrapartum nevirapine (NVP) dosing were randomized to receive orally either single dose NVP alone or NVP plus zidovudine (twice daily for 1 week). An additional group of untreated infants (born to HIV-uninfected women) was enrolled as a control. Laboratory measurements were performed at birth and repeated at 6 weeks of age. Serum alanine aminotransferase (ALT) was measured on approximately 200 infants consecutively enrolled and randomized at the start of the trial. Complete blood count (CBC) was performed on approximately 800 infants at birth and 600 infants at 6 weeks of age. ALT and CBC were also determined on approximately 200 control infants. At birth there were no differences in ALT values between the groups of children. At 6 weeks of age, ALT levels were significantly higher among the treated groups compared with control group (geometric mean of 11.5 U/l for controls and 16.2-19.1 U/l for treated groups; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Hematological parameters did not differ between groups at birth. At 6 weeks of age, levels of hemoglobin, hematocrit, granulocytes, and platelets were significantly (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) lower among antiviral drug-treated groups compared with controls. These changes were consistent with grade 1 (mild) toxicity, and were more noticeable among HIV-infected infants. Hepatic and hematologic abnormalities associated with short-term neonatal antiretrovirals among African children are minimal.
Data on childhood cancers in Africa are sparse, particularly since the spread of HIV. We aimed to... more Data on childhood cancers in Africa are sparse, particularly since the spread of HIV. We aimed to document the frequency of pediatric cancers presenting to a large central hospital in Malawi, detailing the presenting features, initial investigations, and HIV status of these children. A retrospective audit of the spectrum and clinical presentation of cancers among children (&amp;amp;amp;amp;lt;16 years) seen at Queen Elizabeth&amp;amp;amp;amp;#39;s Central Hospital (QECH), between 1998 and 2003. Seven hundred seven children with cancer were seen, the number of cases per year increased over the time period; 50% (351) had Burkitt lymphoma, 13% (89) had retinoblastoma, and 9% (61) had Kaposi sarcoma, with a variety of other tumors comprising the remainder. Kaposi sarcoma markedly increased in frequency over time. Histological verification of diagnosis was available for 49% (348). The proportion of children with cancer who were tested for HIV increased over time, but varied by cancer type. Amongst those tested, the seroprevalence was 93% (52/56) for children with Kaposi sarcoma, 4% (11/289) for those with Burkitt lymphoma, 31% (8/26) for those with other non-Hodgkin lymphomas, 7% (1/15) for those with Hodgkin disease, and 5% (5/103) for those with other cancers. The number of cases seen per year has increased over the study period for almost all cancers, but in particular for Kaposi sarcoma. Burkitt lymphoma remains the commonest pediatric tumor in Malawi. In the case of Burkitt lymphoma, non-Hodgkin lymphoma, and Kaposi sarcoma there is a significant difference in the presentation of HIV-seropositive and -seronegative children.
Journal of health, population, and nutrition, 2005
This prospective study was carried out during February 2000-April 2003 to characterize the relati... more This prospective study was carried out during February 2000-April 2003 to characterize the relationship between the status of carotenoids, vitamin E, and retinol and anthropometric status in apparently healthy infants and their mothers in Blantyre, Malawi. Anthropometric status of infants and concentrations of carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene), retinol, and alpha-tocopherol in plasma were measured in 173 infants at 12 months of age, and concentrations of carotenoids, retinol, and a-tocopherol in plasma were measured in their mothers two weeks postpartum. In multivariate analyses, concentrations of retinol, total carotenoids, non-provitamin A carotenoids, and alpha-tocopherol in infants were associated with under-weight (p = 0.05). Concentrations of a-tocopherol were associated with wasting (p = 0.04). Concentrations in mothers and infants were all correlated (correlation coefficients from 0.230 to 0.502, p < 0.003). ...
We previously reported 57% 12-month event free survival (EFS) in Malawian children with stage I t... more We previously reported 57% 12-month event free survival (EFS) in Malawian children with stage I to III Burkitt lymphoma (BL) with an intermediate dose chemotherapy protocol lasting 77 days. This protocol was shortened to 42 days and evaluated in children with stage I to IV disease for EFS and toxicity. All Malawian children admitted to Queen Elizabeth Central Hospital, from 03/08/2000 to 12/03/2002 with confirmed BL were eligible. A fine needle aspirate, bone marrow aspirate, cerebrospinal fluid cytology, haemoglobin (Hb), white cell count (WCC), malaria smear, ELISA for HIV, and abdominal ultrasound were performed routinely. Murphy staging was used. The first dose of chemotherapy (COP1) consisted of 300 mg cyclophosphamide (CPM), 1 mg vincristine, and 60 mg prednisone given on day 1 and followed by COP2 on day 8 (only for patients with larger tumour volumes, stage III or IV disease). The vincristine dose in COP2 was 2 mg. COMP1 and 2 given on days 22 and 36 consisted of 500 mg CPM, 2 mg vincristine, 60 mg prednisone, and 2 g methotrexate. All doses were calculated per body surface area. Intrathecal methotrexate and hydrocortisone were given with COP1 and 2. Forty-two patients, 30 boys and 12 girls median ages 6 and 7.5 years, respectively, had Murphy stage I(n5), II(n8), III(n21), and IV(n8) disease. The face was involved in 74%, abdomen in 55%, bone marrow in 14%, kidneys in 24%, and 12% had paraplegia. Fourteen children died during or shortly after completion of chemotherapy. Three of these were disease related. Twelve patients suffered a local relapse after 57-328 days, and one a CNS relapse at 76 days. The projected EFS at 12 months is 50% in stage I, 50% in stage II, 24% in stage III, 25% in stage IV, and 33% for all patients. The cumulative mean dose of CPM was 62 mg/kg in survivors and 64 mg/kg in children who relapsed. One third of patients experienced significant marrow suppression, and infections after COMP1. Thirty-three percent of children are in first remission at 12 months. The morbidity and mortality of treatment was high. The high relapse rate in all stages may be due to the low cumulative dose of CPM.
Interferons (IFNs) associated with pregnancy were studied for their possible role in inhibition o... more Interferons (IFNs) associated with pregnancy were studied for their possible role in inhibition of vertical transmission of the human immunodeficiency virus type 1 (HIV-1). A study group was composed of 43 HIV-1-positive mothers, of whom 15 transmitted the virus to the offspring and 28 did not. The control group included 48 HIV-1-negative mother-infant pairs. The IFN-alpha was detected only sporadically in the maternal sera from the groups of transmitters (27%), nontransmitters (21%), and controls (19%). The average levels of IFN-alpha were low, 16.3 +/- 2.5 pg/ml, 21.4 +/- 9.9 pg/ml, and 21.3 +/- 9.4 pg/ml among the transmitters, nontransmitters, and control subjects, respectively. In the cord blood, IFN-alpha was detected only on two occasions among transmitters, and on a single occasion in the control group. IFN-beta was absent from both maternal and cord blood in the study group, and found to be present in one case in the control group simultaneously in the maternal and fetal sera. In the placentas, on the other hand, both type I and II IFNs were expressed universally in the villous trophoblast, and IFN-alpha and -beta in the stromal macrophages as well. In one case among transmitters, no IFNs were detected; nevertheless, no significant difference with respect to nontransmitters could be confirmed. Our data suggest that although the placental IFNs have an antiviral potential, they are not sufficient to suppress transmission of HIV from mother to infant.
to describe the seroprevalence of hepatitis B (HBV) and C (HCV) infection in HIV-positive and HIV... more to describe the seroprevalence of hepatitis B (HBV) and C (HCV) infection in HIV-positive and HIV-negative pregnant women from rural Malawi. descriptive study using serum samples collected between 1993-1995 in the Shire valley in rural Malawi. Fifty HIV-positive and 100 HIV-negative samples were selected randomly from 153 HIV-positive and 443 HIV-negative women delivering in the hospital. evidence of HBV and HCV infection was found in 71.7 and 16.5% of women, respectively. Chronic carriage of HBV (HBsAg positive) is high (13%) and in agreement with prevalences reported from highly endemic areas. Exposure to HBV and HCV probably occurred well before adulthood as the prevalence of anti-HBc antibody was high in young mothers &amp;amp;lt;20 years of age (22/27; 81%). HBV and HCV infections are highly endemic in rural Malawi. There was no statistical evidence to suggest that HIV positivity was associated with an increased prevalence of HBV or HCV markers. Infection with HBV or HCV was not statistically associated.
To measure hepatic and hematological parameters among neonates randomized to receive ultra-short ... more To measure hepatic and hematological parameters among neonates randomized to receive ultra-short antiretroviral regimens. As part of an on-going clinical trial in Malawi, infants born to women who received (early presenters) or did not receive (late presenters) standard intrapartum nevirapine (NVP) dosing were randomized to receive orally either single dose NVP alone or NVP plus zidovudine (twice daily for 1 week). An additional group of untreated infants (born to HIV-uninfected women) was enrolled as a control. Laboratory measurements were performed at birth and repeated at 6 weeks of age. Serum alanine aminotransferase (ALT) was measured on approximately 200 infants consecutively enrolled and randomized at the start of the trial. Complete blood count (CBC) was performed on approximately 800 infants at birth and 600 infants at 6 weeks of age. ALT and CBC were also determined on approximately 200 control infants. At birth there were no differences in ALT values between the groups of children. At 6 weeks of age, ALT levels were significantly higher among the treated groups compared with control group (geometric mean of 11.5 U/l for controls and 16.2-19.1 U/l for treated groups; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Hematological parameters did not differ between groups at birth. At 6 weeks of age, levels of hemoglobin, hematocrit, granulocytes, and platelets were significantly (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) lower among antiviral drug-treated groups compared with controls. These changes were consistent with grade 1 (mild) toxicity, and were more noticeable among HIV-infected infants. Hepatic and hematologic abnormalities associated with short-term neonatal antiretrovirals among African children are minimal.
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