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Malawi is one of the world's poorest countries, but despite this, has a dedicated paediatric oncology service. The service has been hampered by the inability to make a timely cytological diagnosis in the majority of patients. A telemedicine programme was commenced to help overcome this problem, and the results for the first 197 consecutive patients are described. The results are compared with the local reports where available. Most samples were fine needle aspirates (104/197-53%), but others included bone marrow aspirates, peripheral blood films and other fluid collections. A diagnosis was arrived at in 52% of the samples; there were 46 discordant results, 38 were when one or other of the local or distant teams were unable to make a diagnosis, and only 8 where the diagnoses of the 2 teams differed. Diagnoses were made and reports were compiled by the 'distant' team within 24 h and sent to the centre in Malawi. This simple telepathology initiative has had a positive impact on clinical management, and could be used in other less resourced centres twinned with better resourced ones. [ABSTRACT FROM AUTHOR]

Aim: The aim of this retrospective study was to report causes, antibiotic resistance and outcome of neonatal sepsis (often fatal in developing countries) in Malawi. Methods: All blood and cerebrospinal fluid isolates collected between January 1996 and December 2001 from inpatients aged 0–30 days with suspected sepsis at Queen Elizabeth Central Hospital, Blantyre, Malawi were reviewed. In vitro resistance to antibiotics commonly used in Malawi was assessed. Case fatality rate was analysed with respect to age, bacterial pathogen and infection site. Results: A total of 801 bacteria were isolated from 784 neonates over 6 years—599 isolates from blood and 202 from cerebrospinal fluid. Overall, 54% of bacteria were gram-positive and 46% gram-negative. The commonest causes of neonatal sepsis were group B Streptococcus (17%) and non-typhoidal Salmonella (14%). In vitro antibiotic susceptibility to the first-line antibiotic combination of penicillin and gentamicin was 78% for all isolates, but in vitro sensitivities to gentamicin for Klebsiella spp and non-typhoidal Salmonella were only 33% and 53%, respectively. In-hospital case fatality rate was known for only 301 cases and was high at 48%. Group B Streptococcus was associated with the best outcome. Mortality was significantly higher if presentation was in the 1st week of life or if sepsis was caused by gram-negative bacteria. The causes of neonatal sepsis in this population show a different pattern from other studies in developing countries. [ABSTRACT FROM AUTHOR]

In Malawian patients with Kaposi sarcoma (KS) and their relatives, we investigated nucleotide-sequence variation in human herpesvirus-8 (HHV-8) subgenomic DNA, amplified from oral and blood samples by use of polymerase chain reaction. Twenty-four people had amplifiable HHV-8 DNA in 11 sample; 9 (38%) were seropositive for human immunodeficiency virus type 1, 21 (88%) were anti-HHV-8-seropositive, and 7 (29%) had KS. Sequence variation was sought in 3 loci of the HHV-8 genome: the internal repeat domain of open- reading frame (ORF) 73, the KS330 segment of ORF 26, and variable region 1 of ORF K1. Significant intra- person/intersample and intrasample sequence polymorphisms were observed in 14 people (60%). For 3 patients with KS, intraperson genotypic differences, arising from nucleotide sequence variations in ORFs 26 and K1, were found in blood and oral samples. For 2 other patients with KS and for 9 people without KS, intraperson genotypic and subgenotypic differences, originating predominantly from ORF K1, were found in oral samples; for the 2 patients with KS and for 4 individuals without KS, intrasample carriage of distinct ORF K1 sequences also were discernible. Our findings imply HHV-8 superinfection. [ABSTRACT FROM AUTHOR]

Aims-To evaluate the performance of guidelines for emergency triage and treatment (ETAT) of children presenting to hospitals in the developing world. Part of the study was concerned with the delivery of emergency treatment to the sickest group of patients, characterization of their illness, and outcome. Methods and results-A total of 236 children were admitted during the study period, 27 of whom died. The three main causes of death were malaria or malaria related illness (n = 7), pneumonia (n = 6), and malnutrition (n = 11). Forty seven children were categorized as needing emergency treatment. Thirty one had no treatment, and eight died; 16 received one or more recommended treatments, of whom five died. The main limitations to delivery of immediate care were the lack of staff in the department and lack of rapidly available blood. [ABSTRACT FROM AUTHOR]

Sixty-one episodes of Salmonella meningitis were identified during a 3-year period from February 1996 to January 1999 inclusive. These accounted for 6.8% of all the acute bacterial meningitis cases seen during this time. In contrast, only two children were admitted with Salmonella meningitis in 1982. The increase may reflect the rise in HIV disease and the associated increase in Salmonella septicaemia. All but one child were under 2 years of age, only six children were well nourished and anaemia was common. The prognosis was poor: 33 (58%) died, 19 made a full recovery and five developed sequelae. Two children relapsed, one of whom died. Patients were routinely treated with chloramphenicol, to which all isolates were sensitive in vitro . The poor outcomes suggest that an alternative antibiotic policy is required. [ABSTRACT FROM AUTHOR]

Aims: To improve the care of children who are victims of child sexual abuse (CSA) by routinely assessing eligibility for HIV post-exposure prophylaxis (PEP) and to investigate the feasibility, safety, and efficacy of such treatment started in a paediatric emergency department in Malawi. Methods: Children presenting to the Queen Elizabeth Central Hospital, Blantyre between 1 January 2004 and 31 December 2004 with a history of alleged CSA were assessed for eligibility for HIV PEP and followed prospectively for six months. Results: A total of 64 children presented with a history of alleged CSA in the 12 month period; 17 were offered PEP. The remainder were not offered PEP because of absence of physical signs of abuse (n = 20), delay in presentation beyond 72 hours from assault (n = 11), repeated sexual abuse in the preceding six months (n = 15), and HIV infection found on initial testing (n = 1). No family refused an HIV test. No side effects due to antiretroviral therapy were reported. of the 17 children commenced on PEP, 11 returned for review after one month, seven returned at three months, and two of 15 returned at six months post-assault. None have seroconverted. Conclusions: In a resource-poor selling with a high HIV prevalence, HIV PEP following CSA is acceptable, safe, and feasible. HIV PEP should be incorporated in to national guidelines in countries with a high community prevalence of HIV infection. [ABSTRACT FROM AUTHOR]

Limited data address the impact of HIV coinfection on the pharmacokinetics (PK) of antituberculosis drugs in sub-Saharan Africa. A total of 47 Malawian adults underwent rich pharmacokinetic sampling at 0, 0.5, 1, 2, 3, 4, 6, 8, and 24 h postdose. Of the subjects, 51% were male, their mean age was 34 years, and 65% were HIV-positive with a mean CD4 count of 268 cells/μl. Antituberculosis drugs were administered as fixed-dose combinations (150 mg rifampin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol) according to recommended weight bands. Plasma drug concentrations were determined by high-performance liquid chromatography (rifampin and pyrazinamide) or liquid chromatography-mass spectrometry (isoniazid and ethambutol). Data were analyzed by noncompartmental methods and analysis of variance of log-transformed summary parameters. The pharmacokinetic parameters were as follows (median [interquartile range]): for rifampin, maximum concentration of drug in plasma (Cmax) of 4.129 μg/ml (2.474 to 5.596 μg/ml), area under the curve from 0 to 24 h (AUC0-∞) of 21.32 μg/ml · h (13.57 to 28.60 μg/ml · h), and half-life of 2.45 h (1.86 to 3.08 h); for isoniazid, Cmax of 3.97 μg/ml (2.979 to 4.544 μg/ml), AUC0-24 of 22.5 (14.75 to 34.59 μg/ml · h), and half-life of 3.93 h (3.18 to 4.73 h); for pyrazinamide, Cmax of 34.21 μg/ml (30.00 to 41.60 μg/ml), AUC0-24 of 386.6 μg/ml · h (320.0 to 463.7 μg/ml · h), and half-life of 6.821 h (5.71 to 8.042 h); and for ethambutol, Cmax of 2.278 μg/ml (1.694 to 3.098 μg/ml), AUC0-24 of 20.41 μg/ml · h (16.18 to 26.27 μg/ml · h), and half-life of 7.507 (6.517 to 8.696 h). The isoniazid PK data analysis suggested that around two-thirds of the participants were slow acetylators. Dose, weight, and weight-adjusted dose were not significant predictors of PK exposure, probably due to weight-banded dosing. In this first pharmacokinetic study of antituberculosis drugs in Malawian adults, measures of pharmacokinetic exposure were comparable with those of other studies for all first-line drugs except for rifampin, for which the Cmax and AUC0-24 values were notably lower. Contrary to some earlier observations, HIV status did not significantly affect the AUC of any of the drugs. Increasing the dose of rifampin might be beneficial in African adults, irrespective of HIV status. Current co-trimoxazole prophylaxis was associated with an increase in the half-life of isoniazid of 41% (P = 0.022). Possible competitive interactions between isoniazid and sulfamethoxazole mediated by the N-acetyltransferase pathway should therefore be explored further., (Copyright © 2015, van Oosterhout et al.)

Background: A total of 82 % of stationary admissions with the diagnosis of retinoblastoma (2009-2011) to the tertiary ophthalmology unit in Blantyre, Malawi (n = 58) presented with advanced stage disease., Patients and Methods: In another study in 2012 we sought to identify why children mostly presented in advanced stages of disease and whether the delay was unique to children with cancer. In-depth interviews (IDI) were conducted at the hospital with 40 parents or guardians of children with retinoblastoma, congenital cataract, congenital glaucoma and corneal perforation (10 each)., Results: Most delays and delayed admissions occurred at the family (27.5 %, 11 out of 40) and primary health centre levels (30.0 %, 12 out of 40). Lack of money for transport caused delays (15.0 %, 6 out of 40) at all care levels. In contrast, children with painful conditions presented to a health facility within 24 h of onset without any complaints about lack of money for transport., Conclusion: Education about retinoblastoma and other non-painful eye diseases could be improved by a poster campaign to both parents and professionals at all medical healthcare levels. Transport for such cases between the various healthcare centers should be provided free of charge. There is room for improvement in initial diagnosis, referral and management within the healthcare service in the tertiary sector.

We describe five children who died of clinical rabies in a three month period (September to November 2011) in the Queen Elizabeth Central Hospital. From previous experience and hospital records, this number of cases is higher than expected. We are concerned that difficulty in accessing post-exposure prophylaxis (PEP) rabies vaccine may be partly responsible for this rise. We advocate: (a) prompt course of active immunisation for all patients with significant exposure to proven or suspected rabid animals. (b) the use of an intradermal immunisation regime that requires a smaller quantity of the vaccine than the intramuscular regime and gives a better antibody response. (c) improved dog rabies control measures.

Objective: To assess the impact of HIV infection and exposure on survival in critically ill children requiring resuscitation., Methods: A 6-month descriptive prospective cohort study of all live admissions to the resuscitation room of an urban paediatric emergency department in Blantyre, Malawi., Results: 583 children were resuscitated, of whom 401 (69%) survived to hospital discharge. 26% of all children tested positive for HIV infection (152/576), and this was highest in patients presenting with shock (66%; 162/247), clinically diagnosed septicaemia (57%; 125/218) and malnutrition (40%; 24/60). Of 152 HIV-seropositive children, 30 (20%) died within 24 h, while among 424 seronegative children 36 (8.4%) died within 24 h (p<0.001). Later deaths (>24 h) were also more common in HIV-seropositive children compared with HIV-uninfected patients (24.3% vs 12.3%; p<0.001). Survival to 24 h was 80% (122/152) and to discharge 56% (85/152) in HIV-seropositive children. In HIV-uninfected children survival to 24 h was 92% (388/424) and to discharge 79% (336/424)., Conclusion: Early and late case death rates are greater in HIV-seropositive than in HIV-uninfected children. 80% of HIV-infected children survived the period most influenced by the process of resuscitation, that is, the first 24 h. HIV status alone should not influence the limitation of intervention decisions in the resuscitation room when faced with a critically ill child.

Background: To review the results of Wilms' tumour patients in a tertiary referral hospital in a developing country and to find ways of improving long-term survival., Patients and Methods: Between January 1998 and May 2004, 40 patients with Wilms' tumour (WT) were admitted to Queen Elizabeth Central Hospital. Their files were reviewed and general physical condition on admission, pre-operative investigations, management and outcome were noted., Results: The mean age of presentation was 4.2 years with an equal distribution between the sexes. The mean BMI was 15 kg/m2 and more than 80% of the patients were either mildly (PCV <33%) or severely anaemic (PCV <24%). All patients presented with abdominal distension. Half of them had additional complaints including abdominal pain, haematuria, dyspnoea, oedema and or weight loss. Thirty-nine out of the forty patients received pre-operative chemotherapy. Of the 36 patients that underwent surgery, 32 underwent total nephrectomy, one a partial nephrectomy, and in three the tumour was irresectable. There were no intra-operative tumour ruptures. Only 15% of the patients completed their post-operative course of chemotherapy. The 1-year survival lies between 25% and 53%. Fifteen of the 36 patients operated were known to have a recurrence., Conclusion: The patients presented in an advanced stage of the disease. Survival rates are disappointing and recurrence rates are high. Some improvement in outcome may be expected with the implementation of more aggressive treatment protocols but early diagnosis, completion of treatment regimens are needed. Pro-active follow-up is essential to measure outcome.

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.

Background: Screening of children in household contact with smear-positive tuberculosis (TB) is universally recommended but seldom practiced in resource-poor settings. It has huge potential to reduce the burden of TB disease in children, particularly if streamlined to focus on those at greatest risk., Aims: To assess the prevalence of infection and disease amongst children aged < or = 5 yrs in household contact with smear-positive TB. To identify which source case characteristics are risk factors for infection., Methods: A prospective, hospital-based audit was conducted over a 17-mth period in Southern Malawi. Smear-positive adults were identified and encouraged to bring their children to the outpatient clinic, in accordance with the national TB programme guidelines. Full assessment was performed, including tuberculin skin test., Results: 195 children aged < or = 5 yrs who were contacts of 161 source cases were assessed. Prevalences of TB infection and disease were high (45% and 23%, respectively). The likelihood of a child being infected was significantly greater with increasing smear-positivity of the source case, and also if the source case were female (OR 2.25, 95% CI 1.19-4.27, p = 0.01)., Conclusions: The high prevalence of TB infection and disease in child contacts attending this hospital-based clinic supports the current policy of contact-screening in Malawi. However, community-based studies are needed to provide a more accurate assessment of prevalence and risks for child contacts.

Sequence polymorphisms in the gN and gO genes of cytomegalovirus (CMV) amplified from mouth rinse and urine samples of 19 Malawian patients with Kaposi's sarcoma (KS) and 58 of their first-degree relatives were investigated. CMV-DNA was amplified from 41 people (53%) from either the gN or gO region in at least one sample, from 14 people (18%) in both domains in at least one sample, and from 13 (17%) in either domain in both samples. Twenty-one (51%) were seropositive for human immunodeficiency virus-1 (HIV). Identical gN sequences were recovered from eight families and non-identical sequences in six, while identical gO sequences were found in three families and non-identical sequences in five. Five people, four of whom were children, each carried multitypic gN sequences or gO sequences. The findings are consistent with CMV spread along intra- and extra-household routes, and with multiple intra-host CMV infection., ((c) 2005 Wiley-Liss, Inc.)

An integrated care pathway (ICP) is a structured chart that prompts for key observations and interventions in patients to be recorded at set times by medical and nursing staff. ICPs were introduced into the neonatal department of the Queen Elizabeth Central Hospital in Blantyre, Malawi. The number of observations of babies recorded in the year before and 2 years after the introduction of ICPs were compared. When ICPs were in use, 9-96% of the 18 possible daily observations were recorded as having been carried out, compared with 0-33% before their introduction. In the 2nd of the 3 years, there was a fall-off in some observations made, probably because of staff shortages. The ICPs proved effective and easy to use. When adapted to local needs they play an important role in delivering neonatal care.

Aim: To compare presentation, progress, and outcome of acute bacterial meningitis in HIV seropositive and seronegative children., Methods: A double blind randomised placebo controlled study of the use of dexamethasone as adjuvant therapy in acute bacterial meningitis, in children aged 2 months to 13 years, was carried out from July 1997 to March 2001. A total of 598 children were enrolled, of whom 459 were tested for HIV serostatus., Results: Of the 459 children, 34% were HIV seropositive. Their presentation was similar to HIV seronegative children but more were shocked on arrival at hospital (33/157 v 12/302), and more had a focus of infection (85/157 v 57/302). HIV positive children had a higher incidence of Streptococcus pneumoniae infections (52% v 32%). Sixty four cases relapsed; 67% were in HIV positive patients. The mortality in HIV positive children was 65% compared with 36% in HIV negative children. The number of survivors in each group was similar. Hearing loss was more common in HIV negative than HIV positive children (66.3% v 47.2%). Steroid therapy had no influence on meningitis in HIV positive children, but the mortality in HIV negative children was 61% in children given steroids, and 39% in those who did not receive steroids., Conclusion: HIV seropositive children who develop bacterial meningitis have a high mortality and are prone to recurrent disease. There is an urgent need to prevent both primary and recurrent infections.

Background: Steroids are used as adjuvant treatment in childhood pyogenic meningitis to attenuate host inflammatory responses to bacterial invasion. We aimed to assess the effectiveness of dexamethasone in management of acute bacterial meningitis in a developing country., Methods: In a double-blind, placebo controlled trial, we included 598 children with pyogenic meningitis who had been admitted to the children's wards of the Queen Elizabeth Central Hospital, Blantyre, Malawi. We did physical, neurological, developmental, and hearing assessments at 1 and 6 months after discharge. The primary outcome was overall death. Secondary outcomes included sequelae, in-hospital deaths, and death after discharge. Analysis was done by intention to treat., Findings: Of the 598 included children, 307 (51%) were assigned to dexamethasone and 295 (49%) to placebo. 338 (40%) of 598 patients had Streptococcus pneumoniae, 170 (28%) Haemophilus influenzae type b, 66 (11%) Neisseria meningitidis, and 29 (5%) Salmonella spp. 78 (13%) patients had no growth on culture. The number of overall deaths was the same in the two treatment groups (relative risk 1.00 [95% CI 0.8-1.25], p=0.93). At final outcome, sequelae were identified in 84 (28%) of children on steroids and in 81 (28%) on placebo (relative risk 0.99 [95% CI 0.78-1.27], p=0.97). The number of children dying in hospital did not differ between groups., Interpretation: Steroids are not an effective adjuvant treatment in children with acute bacterial meningitis in developing countries.

Objectives: To record the number of children with poisoning admitted to the Queen Elizabeth Central Hospital over one year; to note the causes, clinical and laboratory findings and outcome of each poisoning event and; to highlight any preventable pattern in such events., Design: A one year prospective study was undertaken of all children admitted to the Queen Elizabeth Central Hospital with a history or clinical evidence of acute poisoning. Socio-demographic, clinical and laboratory data were recorded and outcome noted for each child on specially prepared forms. Data were entered and then analysed in Epi-Info 6., Setting: Department of Paediatrics, Queen Elizabeth Central Hospital, Blantyre, Malawi., Interventions: Children were treated forpoisoning according to national guidelines; supportive care and active antidote were given as necessary., Main Outcome Measures: Length of stay in hospital and mortality were primary outcome measures., Results: One hundred and forty four cases were admitted, 118 (82%) were accidental, in 19 cases the reason was unknown and six (4.2%) were non accidental. Carbonate poisoning caused 32% (n=46) of admissions and paraffin 16.7% (n=24). The age range of poisoned children was three weeks to 14 years with a mean of four years and eight months. Eleven deaths occurred, six of which were due to traditional medicine intoxication., Conclusion: Most poisoning were preventable and the public needs to be made aware of the dangers of household agents, advised how to store them in the home and what to do if a child ingests a poisonous substance. Traditional medicines are particularly dangerous to give to infants less than one year old and carry a high mortality.

We report the clinical presentation and outcome of 299 Malawian children with non-typhoidal Salmonella (NTS) bacteraemia and no evidence of focal sepsis, admitted to Queen Elizabeth Central Hospital (QECH), Blantyre, over a 26-month period (February 1996-April 1998). A peak incidence during the rainy season was noted. Salmonella typhimurium (79%) and S. enteritidis (13%) were the commonest isolates. For children aged > 6 months, NTS bacteraemia was significantly associated with malarial parasitaemia (RR 1.5 [1.2, 2.2], P < 0.01) and with severe anaemia (RR 7.2 [3.4, 15.3], P < 0.0001), when compared to other common pathogens causing childhood bacteraemia. Clinical overlap with malaria and anaemia, and the presence of malarial parasitaemia on admission, may delay diagnosis. NTS bacteraemia was commonly diagnosed following blood transfusion. Resistance in vitro to ampicillin (79%), co-trimoxazole (72%) and gentamicin (55%) was very common, and was rare to chloramphenicol (0.3%) which is the antibiotic of choice for NTS sepsis at QECH. Overall mortality was high (23%). Young age and clinical HIV infection were risk factors for mortality. Recurrences of NTS bacteraemia following antibiotic therapy were common among children with clinical HIV infection.