Household carbon monoxide (CO) concentrations in a large African city: An unquantified public health burden?

Carbon monoxide (CO) is a poisonous gas produced by incomplete combustion of carbon-based fuels that is linked to mortality and morbidity. Household air pollution from burning fuels on poorly ventilated stoves can lead to high concentrations of CO in homes. There are few datasets available on household concentrations of CO in urban areas of sub-Saharan African countries. CO was measured every minute over 24 h in a sample of homes in Nairobi, Kenya. Data on household characteristics were gathered by questionnaire. Metrics of exposure were summarised and analysis of temporal changes in concentration was performed. Continuous 24-h data were available from 138 homes. The mean (SD), median (IQR) and maximum 24-h CO concentration was 4.9 (6.4), 2.8 (1.0-6.3) and 44 ppm, respectively. 50% of homes had detectable CO concentrations for 847 min (14h07m) or longer during the 24-h period, and 9% of homes would have activated a CO-alarm operating to European specifications. An association between a metric of total CO exposure and self-reported exposure to vapours >15 h per week was identified, however this were not statistically significant after adjustment for the multiple comparisons performed. Mean concentrations were broadly similar in homes from a more affluent area and an informal settlement. A model of typical exposure suggests that cooking is likely to be responsible for approximately 60% of the CO exposure of Nairobi schoolchildren. Household CO concentrations are substantial in Nairobi, Kenya, despite most homes using gas or liquid fuels. Concentrations tend to be highest during the evening, probably associated with periods of cooking. Household air pollution from cooking is the main source of CO exposure of Nairobi schoolchildren. The public health impacts of long-term CO exposure in cities in sub-Saharan Africa may be considerable and should be studied further.

A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB.

BACKGROUND: Treatment for TB is lengthy and toxic, and new regimens are needed.METHODS: Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6Pa200MZ) or 4 months (4Pa200MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa100MZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation. The non-inferiority margin for between-group differences was 12.0%. Recruitment was paused following three deaths and not resumed.RESULTS: Respectively 4/47 (8.5%), 11/57 (19.3%), 14/52 (26.9%) and 1/53 (1.9%) DS-TB outcomes were unfavourable in patients on 6Pa200MZ, 4Pa200MZ, 4Pa100MZ and controls. There was a 6.6% (95% CI -2.2% to 15.4%) difference per protocol and 9.9% (95%CI -4.1% to 23.9%) modified intention-to-treat difference in unfavourable responses between the control and 6Pa200MZ arms. Grade 3+ adverse events affected 68/203 (33.5%) receiving experimental regimens, and 19/68 (27.9%) on control. Ten of 203 (4.9%) participants on experimental arms and 2/68 (2.9%) controls died.CONCLUSION: PaMZ regimens did not achieve non-inferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority.

Exposure reductions associated with introduction of solar lamps to kerosene lamp-using households in Busia County, Kenya.

Solar lamps are a clean and potentially cost-effective alternative to polluting kerosene lamps used by millions of families in developing countries. By how much solar lamps actually reduce exposure to pollutants, however, has not been examined. Twenty households using mainly kerosene for lighting were enrolled through a secondary school in Busia County, Kenya. Personal PM2.5 and CO concentrations were measured on a school pupil and an adult in each household, before and after provision of 3 solar lamps. PM2.5 concentrations were measured in main living areas, pupils' bedrooms, and kitchens. Usage sensors measured use of kerosene and solar lighting devices. Ninety percent of baseline kerosene lamp use was displaced at 1-month follow-up, corresponding to average PM2.5 reductions of 61% and 79% in main living areas and pupils' bedrooms, respectively. Average 48-h exposure to PM2.5 fell from 210 to 104 µg/m3 (-50%) among adults, and from 132 to 35 µg/m3 (-73%) among pupils. Solar lamps displaced most kerosene lamp use in at least the short term. If sustained, this could mitigate health impacts of household air pollution in some contexts. Achieving safe levels of exposure for all family members would likely require also addressing use of solid-fuel stoves.

Impact of expanded antiretroviral use on incidence and prevalence of tuberculosis in children with HIV in Kenya.

SETTING: Antiretroviral therapy (ART) reduces pulmonary tuberculosis (PTB) in human immunodeficiency virus (HIV) infected children. Recent ART recommendations have increased the number of children on ART. OBJECTIVE: To determine the prevalence and incidence of TB in HIV-infected children after the implementation of expanded ART guidelines. DESIGN: A prospective cohort study including HIV-infected children aged 6 weeks to 14 years was conducted in Kenya. The primary outcome measure was clinically diagnosed TB. Study participants were screened for prevalent TB at enrollment using Kenya's national guidelines and followed at monthly intervals to detect incident TB. Predictors of TB were assessed using logistic regression and Cox proportional hazards regression. RESULTS: Of 689 participants (median age 6.4 years), 509 (73.9%) were on ART at baseline. There were 51 cases of prevalent TB (7.4%) and 10 incident cases, with over 720.3 child-years of observation (incidence 1.4 per 100 child-years). Months on ART (adjusted hazard ratio [aHR] 0.91, P = 0.003; aOR 0.91, P< 0.001) and months in care before ART (aHR 0.87, P= 0.001; aOR 0.92, P < 0.001) were protective against incident and prevalent TB. CONCLUSIONS: ART was protective against TB in this cohort of HIV-infected children with high levels of ART use. Optimal TB prevention strategies should emphasize early ART in children.

ASSOCIATION BETWEEN FINGER CLUBBING AND CHRONIC LUNG DISEASE IN HIV INFECTED CHILDREN AT KENYATTA NATIONAL HOSPITAL.

BACKGROUND: Finger clubbing in HIV infected children is associated with pulmonary diseases. Respiratory diseases cause great morbidity and mortality in HIV infected children. OBJECTIVE: To determine association between finger clubbing and chronic lung diseases in HIV infected children and their clinical correlates (in terms of WHO clinical staging, CD4 counts/percentage, anti-retroviral therapy duration and pulmonary hypertension). DESIGN: Hospital based case control study. SETTING: The Kenyatta National Hospital (KNH) comprehensive care clinic (CCC) for HIV infected children and Paediatric General Wards. SUBJECTS: The study population comprised of HIV infected children and adolescents aged eighteen years and below. RESULTS: Chronic lung disease was more common among finger clubbed (55%) than non finger clubbed patients (16.7%). Finger clubbed patients had higher risk of hypoxemia (46.7%), pulmonary hypertension (46.7%) and advanced disease in WHO stage III/IV (91.7%) compared to non-finger clubbed patients. Finger clubbed patients had lower CD4 cells count and percentage (median 369 cells, 13%) compared to non-clubbed patients (median 861 cells, 28%). Duration of ART use was shorter in finger clubbed patients (median 5.5 months) compared to non-finger clubbed patients (median 40 months). CONCLUSION: Presence of finger clubbing in HIV infected children was associated with chronic lung disease, advanced WHO stage, lower CD4 counts/ percentage, shorter duration of ART use and higher likelihood of developing pulmonary hypertension.

Impact of smear microscopy results and observed therapy on tuberculosis treatment in Mombasa, Kenya.

SETTING: Tuberculosis (TB) treatment center at Coast Provincial General Hospital in Mombasa, Kenya. OBJECTIVES: To describe TB management practices in a facility in coastal Kenya and identify factors associated with poor treatment outcomes. DESIGN: Retrospective review of patient treatment records from January 2008 to June 2009. Treatment outcomes of patients were classified as treatment success (cure or treatment completion) or poor treatment outcome (treatment failure, death or default). Relative risk regression was used to determine the association between exposures of interest and poor treatment outcomes. RESULTS: Records were obtained from a total of 183 patients: 142 (78%) had pulmonary TB, 68 (37%) were human immunodeficiency virus (HIV) infected and 81 (44%) had acid-fast bacilli (AFB) positive smear micros- copy. Most treated individuals (86%) achieved a successful treatment outcome as defined by the World Health Organization. Of those with poor treatment outcomes, 64% defaulted, 32% died, and 4% failed treatment. Initial negative AFB smear and HIV co-infection were associated with poor treatment outcomes (RR 3.32, 95%CI 1.22-8.99 and RR 4.61, 95%CI 1.69- 12.59, respectively). CONCLUSION: Strategies to accelerate accurate diagnosis of smear-negative TB and increase patient retention during treatment, especially in HIV co-infected individuals, are needed to reduce poor treatment outcomes in Kenya.

Oxacillin resistant Staphylococcus aureus among HIV infected and non-infected Kenyan patients.

BACKGROUND: Infections due to methicillin resistant S. aureus (MRSA) present global challenges to clinicians since therapeutic options are limited and suboptimal dosing contributes to heightened mortality and increased length of hospital stay particularly among the HIV infected patients. OBJECTIVES: To assess the prevalence and relative risk of MRSA infections in HIV infected patients. DESIGN: Cross sectional analytical study. SETTING: Kenya Medical Research Institute, Opportunistic Infection Laboratories in Nairobi. SUBJECTS: Four hundred and thirty six male and female patients aged one to 65 years, of whom 220 were HIV-infected and 216 were non-infected. RESULTS: There was 436 male (57.1%) and female (42.9%) respondents. The prevalence of MRSA was 26.3% with majority infecting the HIV infected patients (P=0.046). Likewise, the overall Staphylococcal infections were more common in HIV patients (P <0.001). The common test for MRSA oxacillin disk diffusion had a sensitivity and specificity of 100% and 92%. CONCLUSION: HIV is a predisposing factor to Staphylococcal infection and there are indications that treatment with beta-lactam antibiotics may no longer be relied on as sole empiric therapy for several ill HIV patients whose infections may be of MRSA in origin. There is need for an informed choice in administration of appropriate antibiotics in order to minimise treatment failures due to the multidrug resistance and Vanvomycin intermediate S. aureus (VISA) strains. Molecular epidemiology of MRSA strains in understanding new and emerging trends is recommended.

Multi Drug resistant tuberculosis: a challenge in the management of tuberculosis

Multi drug resistant tuberculosis (MDR-TB) will not usually respond to short course chemotherapy. Unless the individual infected with this bug is treated appropriately; they can continue spreading resistant strains in the community and further fuel the tuberculosis epidemic. Diagnosis requires drug sensitivity testing and the capability to do this is not widely available. Multi drug resistant tuberculosis has been reported all over Africa but the prevalence is still low. The treatment is not only expensive but also quite prolonged and compliance cannot be overemphasized. The recent outbreaks of extensive drug resistant TB further complicate the management and control of the disease. This is a perspective on challenges of managing MDR TB and its effect on the control program the information presented is gathered from published data

Pneumocystis jirovecii and microbiological findings in children with severe pneumonia in Nairobi, Kenya.

OBJECTIVE: To determine the significance of Pneumocystis jirovecii infection in the Kenyan paediatric population. DESIGN: Sixty samples of induced sputum from children aged < or =23 months, half of whom were human immunodeficiency virus (HIV) positive, admitted with severe pneumonia in Nairobi were subjected to immunofluorescent staining for detection of P. jirovecii and microbiological culture. RESULTS: P. jirovecii was detected in 8/60 (13%) as a copathogen with other respiratory pathogens. Five of eight samples with >5 oocysts were from HIV-positive children aged < or =6 months, while equivocally scored samples (< or =5 oocysts) were from HIV-negative children aged >6 months. Klebsiella pneumoniae was significantly recovered in 26/ 60 (43%), followed by Escherichia coli 11/60 (18%) and Staphylococcus aureus 8/60 (13%). Streptococcus pneumoniae, Haemophilus influenzae and Pseudomonas aeruginosa were isolated infrequently. Candida albicans was recovered from 27/60 (45%), while the frequency of C. tropicalis, C. glabrata and C. parapsilosis was 7%, 5% and 3% respectively. Multidrug resistance among E. coli and K. pneumoniae were: sulphamethoxazoletrimethoprim 100% vs. 69%, chloramphenicol 55% vs. 73% and ampicillin 100% vs. 89%. CONCLUSION: Paediatricians in Kenya should be aware of Pneumocystis pneumonia, irrespective of the patient's HIV status.

Prevalence and risk factors of smoking among secondary school students in Nairobi.

OBJECTIVES: To determine the prevalence of smoking and investigate factors that may influence smoking behaviour in secondary school students in Nairobi. DESIGN: Cross-sectional survey in which a self-administered questionnaire was issued to the students. SETTING: Sampled public and private secondary schools in Nairobi. PARTICIPANTS: All the students in the selected secondary schools were included in the study. RESULTS: Five thousand, three hundred and eleven (74.1%) secondary school students were covered. There were 3658 boys and 1653 girls in the study. The mean age was 16.7 years SD +/- 1.48. The study covered 3065 (77.3%) and 2246 (70.1%) of the public and private school students respectively. A total of 1709 (32.2%) were ever-smokers. The overall rate of ever-smoking by gender among the students was 38.6% of males and 17.9% of the females. Experimentation with smoking started at five years and regular smoking at 10 years but majority of students (72.2%) started at between age 12 and 16 years. Parents' and teachers' smoking habits influenced initiation of smoking by young children while peer pressure, advertising and type of school influenced older children to smoking. About 67% of the ever-smokers stopped the habit giving various reasons. There was a strong relationship between age of smoking initiation and stoppage. Majority of the students smoked either to enhance their personalities or for stimulation. Most students smoked less than five cigarettes per day. General shops, kiosks and cigarette stalls which sell cigarettes in both packets and single sticks were the main source to students. Students smoked mostly in the evening and at night. Most student smokers were not discouraged by health warnings on the cigarette packets and awareness of the dangers of smoking. Enforceable legislation that would ban advertising and make smoking illegal was the main recommendation from the students. CONCLUSIONS: Smoking is a problem among Kenyan students. The habit starts quite early in life. Peer pressure, advertising, type of school and age influenced smoking among the students. Banning the sale of cigarettes in single sticks is recommended. Anti-smoking campaigners and specially trained school teachers should encourage attitude shaping among school children towards self confidence and adequacy.

Pneumocystis carinii pneumonia in HIV/AIDS patients at an urban district hospital in Kenya.

BACKGROUND: Pneumocystis carinii pneumonia has generally been regarded to be an uncommon opportunistic infection in HIV infected individuals in sub-Saharan Africa. The reason for this has not been clear but postulates included a lack of suitable pathogenic types in the African environment, diagnostic difficulties and the more commonly held belief that African HIV infected individuals were dying early from common non-opportunistic pathogens before severe degrees of immunosuppression occured. Recently a trend has emerged at the Mbagathi district hospital whereby an increasing number of HIV infected patients are empirically treated for Pneumocystis carinii pneumonia (PCP) based on clinical and radiological features. OBJECTIVE: To determine the prevalence of PCP and clinical outcomes of HIV infected patients presenting at the Mbagathi District Hospital, Nairobi with the presumptive diagnosis of PCP. SETTING: Mbagathi District Hospital, a 169-bed public hospital in Nairobi, Kenya. METHODS: Patients presenting with a sub-acute onset of cough and dyspnoea were eligible for the study if they were found to have bilateral pulmonary shadows and had negative sputum smears for AFBS. Consenting patients who had no contraindication to fiberoptic bronchoscopy had a clinical evaluation which was followed with a fiberoptic bronchoscopy procedure where bronchoalveolar lavage fluid (BALF) was obtained. BALF was examined for cysts of P. carinii using toluidine blue stain and immunofluorescent antibody test (IFAT). BALF was also processed for fungi, bacteria and mycobacteria using routine procedures. Standard treatment with high dose cotrimoxazole was offered to all patients who were then followed up until discharge from hospital or death whichever came first. RESULTS: Between June 1999 and August 2000 a total of 63 patients were referred for bronchoscopy. Of these four declined to undergo the fiberoptic bronchoscopy procedure, four died before the procedure could be done, one was judged too sick to undergo the procedure and three had been on cotrimoxazole for longer than five days. Thus 51 patients underwent bronchoscopy. Pneumocystis carinii stain was positive in 19 (37.2%) while death occured in 16 (31.4%) of the 51 patients. There were more deaths in those without PCP but this difference was not statistically significant (odds ratio 0.68 (95% CI 0.35-1.32; P=0.2). CONCLUSION: PCP was found to be common in HIV infected patients presenting with clinical and radiological features of the disease. The mortality rate for patients with a presumptive diagnosis of PCP is high. This study suggests that cotrimoxazole preventive therapy may be a useful intervention in symptomatic HIV infected patients in Kenya for the prevention of PCP and may avert deaths from this disease.

Antifungal drug susceptibility of Candida albicans.

OBJECTIVE: To determine the susceptibility of clinical isolates of Candida albicans and to establish the minimum inhibitory concentrations (MIC) to commonly used antifungal drugs. DESIGN: Laboratory based experiment. SETTING: Mbagathi District Hospital, Nairobi, Kenya. SUBJECTS: Candida albicans isolated between 1998 and 2000 from the sputa of HIV/AIDS patients and throat swabs of children with acute respiratory infections (ARI). METHODS: Susceptibility to amphotericin B, clotrimazole, nystatin, and 5-fluorocytosine was done using agar dilution method (NCCLS 1997). RESULTS: Among the ARI isolates 29.3% and among HIV isolates 22.4% had MIC>0.5 microg/ml to amphotericin B. Over 80% of the ARI isolates had MICs > 1 microg/ml to clotrimazole. The MIC range of most isolates to nystatin was 4-16 microg/ml while most isolates were susceptible to 5-fluorocytosine. There were no significant differences in susceptibility between ARI and HIV isolates to commonly used antifungal drugs. CONCLUSION: Although fungal resistance has not been extensively studied, susceptibility tests showed some Candida albicans have increased MICs to commonly used antifungal drugs. The results call for further investigations on fungal resistance especially in the context of opportunistic infections in HIV/AIDS.

Chlorproguanil-dapsone: effective treatment for uncomplicated falciparum malaria.

Pyrimethamine-sulfadoxine, the first choice for uncomplicated falciparum malaria in Africa, exerts strong selection pressure for resistance because of its slow elimination. It is likely that resistance will emerge rapidly, and there is no widely affordable replacement. Chlorproguanil-dapsone is cheap, rapidly eliminated, more potent than pyrimethamine-sulfadoxine, and could be introduced in the near future to delay the onset of antifolate resistance and as "salvage therapy" for pyrimethamine-sulfadoxine failure. A total of 448 children were randomly allocated (double blind) to either a single dose of pyrimethamine-sulfadoxine or to one of two chlorproguanil-dapsone regimens: a single dose or three doses at 24-h intervals. Reinfections are clinically indistinguishable from recrudescence and are more likely after treatment with rapidly eliminated drugs; we measured the incidence of parasitemia in 205 initially aparasitemic children to allow comparison with the three treatment groups. The patients and a community surveillance group were followed up for 28 days. At the study end point, 31.2% (95% confidence interval, 24.9-38.0) of the community surveillance group subjects were parasitemic, compared with subjects in the treatment groups, whose rates of parasitemia were 40.8% (32.9-49.0; relative risk [RR], 1.31 [0.99-1.73]) after triple-dose chlorproguanil-dapsone, 19.7% (13.5-27.2; RR, 0.63 [0.43-0.93]) after pyrimethamine-sulfadoxine, and 65.6% (57.5-73.0; RR, 2.10 [1.66-2.65]) after single-dose chlorproguanil-dapsone. Pyrimethamine-sulfadoxine and triple-dose chlorproguanil-dapsone were effective treatments. Pyrimethamine-sulfadoxine provided chemoprophylaxis during follow-up because of its slow elimination. Triple-dose chlorproguanil-dapsone should now be developed in an attempt to reduce the rate of emergence of antifolate resistance in Africa and for affordable salvage therapy in cases of pyrimethamine-sulfadoxine failure.

Chlorproguanil/dapsone for uncomplicated Plasmodium falciparum malaria in young children: pharmacokinetics and therapeutic range.

The disposition of chlorproguanil/dapsone (one daily dose for 3 d of 1.2 and 2.4 mg/kg respectively) has been studied in young children with Plasmodium falciparum malaria, to provide data complementary to a clinical trial of this drug combination. Unbound concentrations of chlorcycloguanil (the active metabolite of chlorproguanil) and dapsone in clinical samples have been related to the unbound drug concentrations which produced defined outcomes in tests in vitro of drug efficacy and toxicity. Twelve children with uncomplicated malaria were treated: all cleared parasitaemia within 72 h and made uneventful recoveries. After the first dose of chlorproguanil/dapsone the maximum unbound chlorcycloguanil concentration in clinical samples (19 ng/mL [about 60 nM]) was 2 orders of magnitude above the 50% inhibitory concentration (IC50) value for this drug against the K39 stain of P. falciparum, while falling 2 orders of magnitude below its IC50 against human bone marrow cells; the maximum unbound dapsone concentration in clinical samples (160 ng/mL [about 645 nM]) was 10-fold higher than its IC50 against the K39 strain. However, because of the rapid elimination of chlorproguanil from the body (half-life 12.6 +/- 6.3 h), the minimum fractional inhibitory concentrations of unbound chlorcycloguanil/dapsone against the K39 strain were probably exceeded for no more than 6 d. These data, together with the clinical trial, will be helpful in deciding whether current chlorproguanil/dapsone doses are optimal for the treatment of falciparum malaria.

Deep breathing in children with severe malaria: indicator of metabolic acidosis and poor outcome.

Despite the frequent association of respiratory symptoms and signs with malarial morbidity and mortality in sub-Saharan Africa, the value of individual symptoms and signs has rarely been assessed. We have prospectively examined the association of individual clinical findings with the summary diagnosis of respiratory distress, outcome, and the presence of metabolic acidosis in children admitted with severe malaria to a Kenyan district hospital. Respiratory distress was present in 119 of the 350 children included in the study and in 23 of the 30 deaths (relative risk = 6.5, 95% confidence interval = 2.8-14.4). The features of a history of dyspnea, nasal flaring, and indrawing or deep breathing (Kussmaul's respiration) were individually most closely associated with the summary diagnosis of respiratory distress. Of these, deep breathing, which was sensitive (91%) and specific (83%) for the presence of severe metabolic acidosis (base excess < or = -12), is the best candidate sign to represent the prognostically important syndrome of malarial respiratory distress. Therefore, it warrants further prospective evaluation in different clinical settings and areas of different malaria endemicity.

Chronic salicylate poisoning and severe malaria.

BACKGROUND Salicylates continue to be marketed and to be used in developing countries as over-the-counter (OTC) antipyretics in children, whereas in developed countries they are no longer used in children because of safety concerns. The presenting signs of salicylate poisoning, especially chronic (repeated administration of therapeutic or excessive doses for longer than 12 h), can include metabolic acidosis, hypoglycaemia, lethargy, and coma and fits. These signs are also common in severe malaria in African children. Admission of two probable cases of chronic salicylate poisoning prompted us to look for other cases among children presenting to our hospital in Kenya, apparently with severe malaria. METHODS All children admitted to Kilifi District Hospital between July and September, 1994, who had a positive blood film for Plasmodium falciparum, and one or more of coma, prostration, or respiratory distress were eligible. As well as routine tests for malaria and routine biochemistry, salicylate concentrations were measured. Management of children (aged 6 months to 10 years) in the community was assessed by a cross-sectional survey of 463 households and by interviews with mothers 2 days after they had bought OTC drugs for a child with fever. FINDINGS Data were available for 143 of 154 children with initial primary diagnoses of severe malaria. 129 (90 percent) had detectable (>l mg/dL) salicylate. Six of these had salicylate concentrations of 20 mg/dL or higher. All six had neurological impairment and metabolic acidosis and four were, or became, hypoglycaemic. OTC drugs were the first-line treatment in 188 (74 percent) of 254 fever episodes during the 2 weeks before the cross-sectional survey. Of 250 mothers who bought drugs for a febrile child, 236 (94 percent) bought a preparation containing salicylates and 50 (21 percent) gave a dose higher than the manufacturer's recommended maximum. INTERPRETATION These cases suggest that in some children salicylate poisoning may cause or contribute to the development of metabolic acidosis and hypoglycaemia, complications of severe malaria associated with high mortality.

An open randomized trial of artemether versus quinine in the treatment of cerebral malaria in African children.

We have compared the efficacy of artemether versus quinine as treatment for cerebral malaria in children in an open randomized clinical trial in Kenya. Children admitted to hospital with coma and Plasmodium falciparum parasitaemia were treated with either intramuscular artemether (3.2 mg/kg loading dose followed by 1.6 mg/kg daily) or intravenous quinine (20 mg/kg loading dose followed by 10 mg/kg every 8 h). Both drugs were well tolerated and no significant adverse effect was observed. Parasite clearance times (50% and 90%) were shorter in patients treated with artemether (median times [h], with interquartile ranges in brackets, were: 50%, 7.3 [4.2-12.4] vs. 15.5 [9-22]; 90%, 16.9 [13.2-25] vs. 28.5 [22-35]; P < 0.0001). The total mortality in 160 children with cerebral malaria was 16.25%, with no overall significant difference between the 2 treatment groups. In a subgroup of children with respiratory distress, mortality was higher in those treated with artemether (43.7% vs. 11.1%, P < 0.05). The frequency of neurological sequelae and clinical recovery times were similar in both treatment groups. We conclude that there would currently be no advantage in replacing quinine with artemether for the treatment of cerebral malaria in African children.

The management of severe malaria in children: a review.

We have attempted to summarise an approach to management of severe malaria from our experience and that of others from published data in this review. This represents our current state of knowledge and practices which may change as research continues in this field. It also represents what we feel should be the minimum aim in treating severe malaria even at district hospital level. It focuses on practical issues encountered when admitting such patients: initial assessment, immediate supportive management, use of transfusion, appropriate anti-malarial treatment and ongoing management.