Incidence of childhood cancer in Latin America and the Caribbean: coverage, patterns, and time trends / Incidencia del cáncer infantil en América Latina y el Caribe: cobertura de los registros, patrones y tendencias a lo largo del tiempo / Incidência de câncer infantil na América Latina e no Caribe: cobertura, padrões e tendências temporais

ABSTRACT Objective. To provide a comprehensive overview of geographical patterns (2001-2010) and time trends (1993-2012) of cancer incidence in children aged 0-19 years in Latin America and the Caribbean (LAC) and interpret the findings in the context of global patterns. Methods. Geographical variations in 2001-2010 and incidence trends over 1993-2012 in the population of LAC younger than 20 years were described using the database of the third volume of the International Incidence of Childhood Cancer study containing comparable data. Age-specific incidence per million person-years (ASR) was calculated for population subgroups and age-standardized (WSR) using the world standard population. Results. Overall, 36 744 unique cases were included in this study. In 2001-2010 the overall WSR in age 0-14 years was 132.6. The most frequent were leukemia (WSR 48.7), central nervous system neoplasms (WSR 23.0), and lymphoma (WSR 16.6). The overall ASR in age group 15-19 years was 152.3 with lymphoma ranking first (ASR 30.2). Incidence was higher in males than in females, and higher in South America than in Central America and the Caribbean. Compared with global data LAC incidence was lower overall, except for leukemia and lymphoma at age 0-14 years and the other and unspecified tumors at any age. Overall incidence at age 0-19 years increased by 1.0% per year (95% CI [0.6, 1.3]) over 1993-2012. The included registries covered 16% of population aged 0-14 years and 10% of population aged 15-19 years. Conclusions. The observed patterns provide a baseline to assess the status and evolution of childhood cancer occurrence in the region. Extended and sustained support of cancer registration is required to improve representativeness and timeliness of data for childhood cancer control in LAC.

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RESUMO Objetivo. Apresentar uma visão abrangente dos padrões geográficos (2001 a 2010) e das tendências temporais (1993 a 2012) da incidência de câncer em crianças e jovens de 0 a 19 anos na América Latina e no Caribe (ALC) e interpretar os resultados no contexto de padrões mundiais. Métodos. Foram descritas variações geográficas de 2001 a 2010 e tendências de incidência de 1993 a 2012 na população com menos de 20 anos da ALC usando informações comparáveis da base de dados do terceiro volume do estudo International Incidence of Childhood Cancer. Foram calculadas taxas de incidência específica por idade por milhão de pessoas-ano (ASR, na sigla em inglês) para subgrupos populacionais e taxas padronizadas por idade usando a população padrão mundial (WSR, na sigla em inglês). Resultados. No total, foram incluídos 36 744 casos únicos. No período de 2001 a 2010, a WSR para todos os tumores combinados na faixa etária de 0 a 14 anos foi de 132,6. Os diagnósticos mais frequentes foram leucemia (WSR de 48,7), neoplasias do sistema nervoso central (WSR de 23,0) e linfoma (WSR de 16,6). A ASR para todos os tumores combinados na faixa etária de 15 a 19 anos foi de 152,3, e a maior taxa foi a de linfoma (ASR de 30,2). A incidência foi maior no sexo masculino do que no sexo feminino e maior na América do Sul do que na América Central e no Caribe. De modo geral, em comparação com as estimativas mundiais, a incidência na ALC foi menor, exceto para leucemia e linfoma entre 0 e 14 anos e para outros tumores e tumores não especificados em qualquer idade. A taxa de incidência na faixa etária de 0 a 19 anos aumentou em 1,0% ao ano (IC de 95% [0,6, 1,3]) entre 1993 e 2012. Os registros incluídos cobriam 16% da população de 0 a 14 anos e 10% da população de 15 a 19 anos. Conclusões. Os padrões observados servem de referência para avaliar o status e a evolução da ocorrência de câncer infantil na região. É necessário garantir um apoio ampliado e consistente aos registros de câncer para aprimorar a representatividade e a disponibilidade das informações em tempo adequado para o controle do câncer infantil na ALC.

Burkitt's lymphoma: The prevalence of HIV/AIDS and the outcome of treatment.

The prevalence of HIV in Burkitt's lymphoma (BL) patients and the outcome of treatment in Cameroon were unknown. Records of all patients diagnosed with BL at three Cameroon Baptist Convention hospitals were reviewed to ascertain the recorded HIV status and outcome of treatment. Of 979 patients diagnosed with BL, 717 were tested for HIV and 11 (1.5%) were HIV-positive. Three of eight patients treated with both cyclophosphamide (CPM)-based chemotherapy and antiretrovirals were alive at 62, 96 and 111 months, respectively. The HIV rate was comparable to that of 1% for the general population of children aged <15 years. Low-cost high-frequency CPM was the only available treatment option for BL and was associated with 37.5% long-term survival in a resource-limited setting.

Kaposi's sarcoma: Good outcome with doxorubicin, bleomycin and vincristine sulphate (ABV) chemotherapy and highly active antiretroviral therapy.

There is little published information on effective treatment of Kaposi's sarcoma (KS) in children in low-income countries. We prospectively treated 12 patients with an institutional review board-approved protocol consisting of four monthly courses of doxorubicin (Adriamycin), bleomycin and vincristine sulphate (ABV), with highly active antiretroviral therapy (HAART) plus co-trimoxazole prophylaxis for those who were HIV-positive, with additional vincristine if remission was not achieved after 4 months. Maintenance HAART plus co-trimoxazole was given to all HIV-positive patients. A fine-needle aspirate and CD4+ count were done if possible, and staging was performed according to Mitsuyasu. Eight of ten HIV-positive patients with stage III - IVB disease, and both HIV-negative patients with stage I disease, were in remission after 473 - 1 490 (mean 939) days. One patient died after absconding during treatment, and one died from neutropenia-related pulmonary infection. ABV with or without HAART is an effective treatment option for children with KS.

Burkitt's lymphoma patients in Northwest Cameroon have a lower incidence of sickle cell trait (Hb AS) than healthy controls.

Contradictory findings have been reported from Africa with regard to the risk of developing Burkitt's lymphoma (BL) in sickle cell trait (AS)carriers. Haemoglobin electrophoresis was performed in 78 BL patients in the Northwest region of Cameroon, and in 78 nearest-neighbourcontrols of the same age, sex and tribe from the same village. AS was confirmed in 4 of 78 (5.13%) BL patients and in 11 of 78 (14.10%)controls (χ2, p=0.052; Fisher's exact, one-tailed, p=0.050). Sickle cell trait carriers had a marginal statistically reduced risk of developing BL.

Substrain and light regime effects on integrated anxiety-related behavioral z-scores in male C57BL/6 mice-Hypomagnesaemia has only a small effect on avoidance behavior.

Magnesium (Mg) has been described to possess an anxiolytic function, but a number of studies present inconsistent results on this matter. In this study the effect of Mg deficiency on anxiety-related behavior, brain and blood plasma Mg in young adult male C57BL/6JOlaHsd and C57BL/6NCrl mice was studied. The animals were put on a control or Mg deficient diet from day 0 and significant hypomagnesaemia was evident from day 12 onwards in the test animals. Housing and test conditions were under either conventional light regime (white light behavioral test conditions) or reverse light regime (red light behavioral test conditions). The animals were tested in three tests for unconditioned anxiety: the modified Hole Board (day 14), the light-dark test (day 21) and the elevated plus maze (day 28). Overall integrated behavioral z-scores were calculated over these three behavioral tests. Mg showed a structure dependent distribution at the level of the brain, that differed between C57BL/6 substrain and light regime (conventional versus reverse), respectively. Likewise, total brain Mg did differ between substrain and light regime, but was not affected by the diet. Animals on the Mg deficient diet housed under conventional light regime had a higher final (day 28) blood plasma corticosterone level as compared to controls. Animals housed under reverse light regime exhibited no diet effect of plasma corticosterone levels. The significant hypomagnesaemia at blood plasma level resulted in an effect of Mg deficiency on avoidance, but not overall anxiety-related behavior. Significant differences regarding avoidance behavior were found between the two substrains and light regimes, respectively.

Endemic Burkitt Lymphoma: Long-term Outcome in 87 Patients Who Presented With Paraplegia in Cameroon.

The reported long-term outcome of endemic Burkitt lymphoma (eBL) patients who present with paraplegia is largely unknown. Records of BL patients treated with comparable short-interval cyclophosphamide chemotherapy schedules between 2004 and 2014 at three Baptist mission hospitals in Cameroon were reviewed. Survivors were followed up and examined at home or in hospital. Eighty-seven of 948 (9.2%) patients had paraplegia at diagnosis. The survival rate in eBL patients with paraplegia at diagnosis was 33% (n = 29) after follow-up of between 2 and 96 (median 40) months. Seven patients (24%) had neurological sequelae and needed rehabilitation. There was no relationship between the duration of symptoms (<2, 2-4, >4 weeks) and the survival rate or the risk to have neurological sequelae. The survival rate and risk for sequelae were similar in patients with confirmed St. Jude stage III and IV diseases.

Epidemiology of Burkitt's lymphoma in Northwest Province, Cameroon, 2003-2010.

BACKGROUND: Burkitt's lymphoma (BL) is an aggressive non-Hodgkin's lymphoma endemic to regions of Africa. Cases are thought to be typically found in low-lying, humid regions where malaria is rife. AIMS AND OBJECTIVES: To investigate the clinical characteristics of BL, its incidence and relationship with malarial incidence in Northwest (NW) Province, Cameroon. METHODS: Data on BL were collected from the three tertiary referral centres for BL treatment in NW Province, Cameroon. Data on malaria were collected from the Delegation of Public Health in Bamenda, NW Province. Data were collected between March and May 2010. RESULTS: 471 cases of BL were identified. The St Jude's stage of patients at presentation was as follows: stage I, 14.4% (43/299); stage II, 8.4% (25/299); stage III, 69.9% (209/299); stage IV, 7.4% (22/299). The incidences of BL per 100,000 children <15 years of age from 2005 to 2009 were as follows: 2005, 3.01 (29); 2006, 2.02 (20); 2007, 2.45 (25); 2008, 2.38 (25); 2009, 3.06 (33). The average incidence in NW Province was 2.58. In the Ndop plain, Ngo-Ketunjia, the incidences of BL were as follows: 2005, 10.3 (10); 2006, 3.00 (3); 2007, 1.95 (2); 2008, 2.84 (3); 2009, 4.60 (5). The average incidence was 4.54/100,000 children <15 years of age. Statistical analysis demonstrated a sinusoidal distribution of malaria cases throughout the year (P<0.00), with a peak incidence on 10 April. Conversely, no sinusoidal distribution of BL cases was demonstrated throughout the year (P = 0.09). CONCLUSION: No relationship was demonstrated between an acute malarial infection and BL. Significant clustering was found, with the low-lying Ndop plain of Ngo-Ketunjia having an incidence of BL nearly twice that elsewhere in the region. The study demonstrates that the incidence of BL in NW Province, Cameroon remains one of the highest documented in the world.

The Cameroon 2008 Burkitt lymphoma protocol: improved event-free survival with treatment adapted to disease stage and the response to induction therapy.

Treatment of endemic Burkitt lymphoma (BL) with cyclophosphamide (CPM) and intrathecal methotrexate (IT MTX) can cure 50% of patients. In this study, induction therapy with CPM and IT MTX was followed by consolidation chemotherapy adapted for stage, clinical response, and abdominal ultrasound findings. One hundred and twenty-nine consecutive patients with BL, 77 male and 52 female with a median age of 7.9 years, were treated in mission hospitals in Cameroon. The diagnosis rested on fine-needle aspirate (79%), biopsy, bone marrow, cerebrospinal fluid, abdominal ultrasound, and clinical examination. Six percent had St Jude stage I, 13% stage II, 72% stage III, and 12% stage IV disease. The abdomen (76%) and face (50%) were mainly involved. Induction chemotherapy was CPM 40 mg/kg and IT MTX 12.5 mg and IT hydrocortisone 12.5 mg on days 1, 8, and 15. Stage I and II patients received CPM 60 mg/kg on day 29, and stage III patients CPM 60 mg/kg on days 29 and 43 if in remission on day 28. Stage IV patients and patients not in remission received CPM 60 mg/kg on days 29, 43, and 57 and 1.0 g/m(2) MTX intravenous (IV) and vincristine 1.5 mg/m(2) IV on day 29. Event-free survival (EFS) at mean 365 days was 61% (n = 79) and 100% in stage I, 85% in stage II, 60% in stage III, and 27% in stage IV patients. Deaths (n = 24) were disease or treatment related and 26 patients relapsed (mean 135 days). Risk-adapted treatment achieved 61% 1-year EFS.

The use of ultrasound in endemic Burkitt lymphoma in Cameroon.

BACKGROUND: As ultrasound (US) has become more widely available in sub-Saharan Africa, emerging evidence suggests that the prevalence of abdominal disease in endemic Burkitt lymphoma (eBL) is higher than previous estimates. This retrospective chart review was designed to assess: (1) abdominal US utilisation, (2) the incidence of abdominal disease at diagnosis, (3) correlation of extent of disease at diagnosis with overall and event-free survival (EFS). PROCEDURE: The charts of 95 consecutive children with eBL diagnosed between April 2006 and 2008 and treated according to the Malawi 2002/03 protocol at the Banso Baptist Hospital in Cameroon were examined for demographics, clinical presentation, diagnostic workup and outcome. Analysis was performed using descriptive statistics, Z-tests and Student's t-tests. RESULTS: Fifty of 95 presumptive eBL patients (52.7%) had fine needle aspirate (FNA) confirmation of their tumours. Ninety-four of 95 had an US at diagnosis. US was superior to clinical exam in demonstrating abdominal disease (P < 0.001). There was no significant difference between the rates of jaw (73%) and abdominal disease (82%) identified by US at diagnosis. EFS among patients whose disease was upgraded by US (64%) was better that of the patients with clinically diagnosed stage 3 disease. CONCLUSIONS: We demonstrate that US provides more accurate staging of eBL than clinical examination. Abdominal involvement is more common than previously reported and appears to be as frequent as disease of the jaw at presentation. Further study should determine if more accurate staging with US is useful in risk-stratifying treatment.

The incidence, clustering and characteristics of Burkitt lymphoma in the Northwest province of Cameroon.

The epidemiology of Burkitt lymphoma (BL) has never been documented in Cameroon. Data were collected from 16 hospitals, the Delegation of Public Health and the regional pathologist in the Northwest province of Cameroon on all BL cases. The incidence of BL in this region is 5.9/100,000 children aged <15 years/year - the second highest incidence documented to date. Significant clustering was also identified in Ndop, a low-lying region with a high malaria endemicity, at 21.5 cases/100,000 children aged <15 year/year (P < 0.001).

Endemic Burkitt lymphoma: a 28-day treatment schedule with cyclophosphamide and intrathecal methotrexate.

BACKGROUND: Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in equatorial Africa and there is a need for affordable, effective treatment. AIM: To record the morbidity of treatment and event-free survival after 1 year using relatively high doses of cyclophosphamide at short intervals combined with intrathecal methotrexate. METHODS: Forty consecutive patients with a mean age of 6.9 (range 2-15) years were treated at Queen Elizabeth Central Hospital, Blantyre between 10th April and 17th November 2006. The initial diagnosis was made clinically and confirmed by fine-needle aspiration in 73%. Abdominal ultrasound, bone marrow aspirate and CSF analysis were undertaken routinely. Chemotherapy consisted of cyclophosphamide, 40 mg/kg on day 1 and 60 mg/kg on days 8, 18 and 28. Intrathecal methotrexate 12.5 mg and hydrocortisone 12.5 mg were administered on days 1, 8, 18 and 28. Allopurinol was commenced before chemotherapy, and a high urinary output was maintained to prevent tumour lysis. RESULTS: St Jude stage distribution was stage I, 1; II, 9; III, 24; and IV, 6. An equal number (70%) presented with abdominal and facial disease, and 15% with paraplegia. Twenty patients (50%) were below the 5th NCHS centile for weight-for-age. Two patients died during treatment, three had chemotherapy-resistant disease and 35 (88%) achieved complete clinical remission by day 28. Sixteen required antibiotic treatment for presumed infection and nine received a blood transfusion. Relapse occurred in 16 patients after 65-311 days (median 137). Nineteen patients (48%) have been in continued remission for 265-670 days (median 454). CONCLUSION: This short, inexpensive treatment schedule (<50 US$) cured almost 50% of eBL patients in a setting of very limited resources.

The effect of vitamin A status in children treated for cancer.

Chemotherapy for cancer can cause immunocompromise. The authors speculated that children with cancer and low vitamin A plasma levels were more susceptible to cancer treatment-related complications than children who are not vitamin A deficient. A cohort of 49 children with cancer were followed from diagnosis until death or for at least 5 years. Plasma retinol levels were determined at diagnosis. Complications of treatment were recorded. Children with low retinol levels at diagnosis tended to have more chance to develop febrile neutropenia (p = .052). Children with fever had lower mean vitamin A levels at diagnosis than those who did not suffer febrile episodes. In a childhood population with a high prevalence of vitamin A deficiency, routine vitamin A assessment and supplementation in children with cancer appears indicated.

Rescue chemotherapy for patients with resistant or relapsed endemic Burkitt's lymphoma.

Patients with endemic Burkitt's lymphoma who failed primary treatment with the Malawi 2002 or 2003 Burkitt's lymphoma treatment protocols, consisting of high frequency cyclophosphamide 40 mg/kg and intrathecal methotrexate, were offered rescue chemotherapy. Twenty-eight patients (14 boys and 14 girls; age range 3-13 years) with resistant disease (n=8) or relapse (n=20) presented to the Queen Elizabeth Central Hospital, Blantyre, Malawi. Treatment consisted of cyclophosphamide 60 mg/kg and vincristine 1.5 mg/m(2) i.v. on Days 1, 8 and 15, plus intrathecal methotrexate on the same days in those patients treated for a relapse. The majority of patients (81%) had St Jude stage III or IV disease. Twenty patients (71%) achieved a complete clinical remission. Day 8 treatment was delayed in eight children and Day 15 treatment in five patients, both for a median of 7 days, mainly due to neutropenia. Ten patients relapsed after 42-311 days (median 105 days). Ten patients (36%) remained in remission for 353-712 days (median 487 days). Patients whose first relapse occurred after 6 months as well as those with limited disease had the best outcome. This simple 15-day chemotherapy schedule salvaged 36% of patients and significantly increased the overall cure rate of our Burkitt's lymphoma patients.

Viral Infections In Children Receiving Anticancer Chemotherapy

OBJECTIVE: To determine the presence of bacterial and viral infectious agents in children with fever during anticancer chemotherapy. DESIGN: Analysis of data obtained during a prospective cohort study. SETTING: The pediatric oncology unit of Tygerberg Children's Hospital; Cape Town. SUBJECTS: All patients up to the age of 15 years who deve- loped fever secondary to anticancer chemotherapy from February 9th 2000 to April 9th 2001. OUTCOME MEASURES: Viruses were isolated or antigens detected on venous blood samples; nasopharyngeal aspirates; throat swabs; urine and feces where possible. Blood for aerobic and anaerobic culture was obtained from an indwelling intravenous catheter and/or a peripheral vein. RESULTS: Thirty-four children were analyzed for a total of 102 febrile episodes. The absolute neutrophil count on admission was below 0.5*109/L in 57 (56) episodes and thus considered neutropenic. Thirty-five viral isolates were identified in 31 (30) febrile episodes: HSV-1 (n=14); HSV-2 (n=2); CMV (n=10); rotavirus (n=5); adenovirus (n=2); Para influenza type 3 (n=1) and hepatitis B (n=1). The blood culture was positive in 24 (24) febrile episodes. Within these; a combined viral and bacterial infection was demonstrated in 6 (6) episodes. Infections were more frequent in neutropenic compared to non-neutropenic episodes; however; this was not significant. CONCLUSIONS: Viral infections clearly are an important cause of fever in children receiving anticancer therapy and may occur together with a bacterial infection. Diagnostic tests for viral infections should be used more frequently and could be of considerable value in evaluating fever and establishing appropriate treatment in these patients

Spectrum and presentation of pediatric malignancies in the HIV era: experience from Blantyre, Malawi, 1998-2003.

BACKGROUND: 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. PROCEDURE: 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. RESULTS: 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. CONCLUSIONS: 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.

The Changing Face of Neonatal Intensive Care in South Africa

In 1991 a cut-off weight of 1 000 g and/or 28 weeks' gestation for neonatal intensive care unit (NICU) admission was decided on by attending neonatologists at a Priorities in Perinatal Care Conference. These recommendations were not based on published evidence. At the time there were few data on the outcome of babies born in the public sector who received NICU. Aim. The aim of this study was to describe the demographic data (mother and baby) and outcomes of babies admitted to a tertiary NICU. Methods. During 1992 - 1996 (1992 cohort) and 1999 - 2000 (1999 cohort) two cohorts of babies treated in the NICU at Tygerberg Hospital; Western Cape; South Africa; were studied. Demogra- phic data were collected prospectively on all admissions with a birth weight of less than 1 501 g and a gestational age of less than 32 weeks. Outcome data were survival; days of ventilation and NICU stay. Results. There were 455 babies in the 1992 cohort and 272 in the 1999 cohort. The mothers' mean income was R892 per month and was higher in the 1999 cohort.The 1999 cohort comprised significantly smaller babies; at a mean birth weight of 1 119 g v. 1 198 g. The mean gestational age in the 1999 cohort was lower (29.2 v. 30.3 weeks); but so was the mortality rate (21.6v. 26.1). The main differences between the survivors and non-survivors were in their birth weight and gestational age and the mean income of their mothers. The mean number of ventilation days needed by these infants was low at 8.5 days; with an average stay in the NICU of 13 days. Discussion. Babies admitted to an NICU have a good chance of survival at a low mean number of ventilation and NICU days. The increase in survival in the 1999 cohort; in spite of low income; is in keeping with international trends and underlines the good short-term outcome of these small babies

Improved outcome in South African children of mixed ethnicity treated for all.

A historical cohort study with an analytical component was conducted to determine whether risk-appropriate chemotherapy can improve survival in children of mixed ethnicity with ALL. Eighty-one coloured children treated for ALL in South Africa were divided into 2 groups: group A (n = 39), treated prior to 1992, and group B (n = 42), treated after 1992. A comparison was made of survival, treatment complications, and supportive measures. The two groups were comparable. The mean nadirs of the white cell count (p < .01), platelet count (p = .01), and hemoglobin value (p < .01) were significantly lower in group B. The survival rate of 37% in group A improved to 66% in group B (p = .025). The results show that a risk-adapted regimen increased survival in children of mixed ethnicity in the Western Cape, despite increased hematological toxicity and episodes of febrile neutropenia.

Isoniazid pharmacokinetics in children treated for respiratory tuberculosis.

AIMS: To define the pharmacokinetics of isoniazid (INH) in children with tuberculosis in relation to the N-acetyltransferase 2 (NAT2) genotype. METHODS: The first order elimination rate constant (k) and area under the concentration curve (AUC) were calculated in 64 children <13 years of age (median 3.8) with respiratory tuberculosis from INH concentrations determined 2-5 hours after a 10 mg/kg INH dose. The NAT2 genotype was determined; 25 children were classified as homozygous slow (SS), 24 as heterozygous fast (FS), and 15 as homozygous fast (FF) acetylators. RESULTS: The mean (SD) k values of the genotypes differed significantly from one another: SS 0.254 (0.046), FS 0.513 (0.074), FF 0.653 (0.117). Within each genotype a median regression of k on age showed a significant decrease in k with age. The mean (SD) INH concentrations (mg/l) two hours after INH administration were SS 8.599 (1.974), FS 5.131 (1.864), and FF 3.938 (1.754). A within genotype regression of 2-hour INH concentrations on age showed a significant increase with age. A within genotype regression of 3-hour, 4-hour, and 5-hour concentrations on age also showed a significant increase with age in each instance. In ethnically similar adults, mean (SD) 2-hour INH concentrations (mg/l) for each genotype were significantly higher than the children's: SS 10.942 (1.740), FS 8.702 (1.841), and FF 6.031 (1.431). CONCLUSIONS: Younger children eliminate INH faster than older children and, as a group, faster than adults, and require a higher mg/kg body weight INH dose to achieve serum concentrations comparable to adults.