Familial Hydrocephalus and Dysgenesis of the Corpus Callosum Associated with Xp22.33 Duplication and Stenosis of the Aqueduct of Sylvius with X-Linked Recessive Inheritance Pattern.

INTRODUCTION: X-linked recessive mutations predominantly affect male fetuses with milder or no abnormalities in female siblings. Most reports show only one affected member in the family. We are reporting a family affected with hydrocephalus, stenosis of the aqueduct of Sylvius, dysgenesis of the corpus callosum, and Xp22.33 microduplication. CASE PRESENTATION: Eighteen-year-old patient was evaluated for her 2 pregnancies; the first was a male fetus with severe hydrocephalus and the second a female fetus with mild hydrocephalus. Postnatal MRI evaluation of the male neonate revealed stenosis of the aqueduct of Sylvius, dysgenesis of the corpus callosum, and severe hydrocephalus requiring ventriculoperitoneal shunt. Postnatal MRI evaluation of the female neonate revealed mild hydrocephalus, stenosis of the aqueduct of Sylvius, and mild dysgenesis of the corpus callosum. The female baby did not require surgical intervention. Genetic testing of the mother and the 2 children revealed a 439 Kb duplication of Xp22.33. DISCUSSION: This family demonstrates typical X-linked recessive heritability. X-inactivation is a compensatory mechanism that explains the mild symptoms of the female child and the severe symptoms of the male child. This familial case shows the importance of prenatal testing and genetic counseling and testing, including karyotype and chromosomal microarray.

A new complex homozygous large rearrangement of the PINK1 gene in a Sudanese family with early onset Parkinson's disease.

PARK2 and PINK1 gene mutations are involved in recessive early onset Parkinson's disease (EOPD). In order to determine the causative mutations in three affected sibs from a consanguineous Sudanese family with EOPD, multiplex ligation-dependent probe amplification was performed and revealed that the patients were homozygous for a deletion of PINK1 exons 4 to 8. Breakpoint analysis revealed a complex rearrangement combining a large deletion and the insertion of a sequence duplicated from the DDOST gene intron 2, located near the PINK1 gene. As breakpoint sequences displayed only three base pairs of homology, this rearrangement may result from Fork Stalling and Template Switching mechanism. This third large rearrangement of PINK1 enlarges the mutation spectrum and, together with recent published data in Tunisian patients with EOPD, points out that PINK1 gene analysis, including search for large rearrangement, should be considered in early onset recessive PD patients, particularly those from Arab origin.

Perinatal outcomes following Helping Babies Breathe training and regular peer-peer skills practice among village midwives in Sudan.

BACKGROUND: Over 80% of deliveries in Sudan occur in rural areas, attended by village midwives (VMWs). OBJECTIVE: To determine the impact of Helping Babies Breathe training and regular peer-peer skills practice (HBBT+RPPSP) on VMW resuscitation practices and outcomes. METHODS: In a prospective community-based intervention study, 71/82 VMWs, reporting to six East Nile rural medical centres, with previous experience in community health research, consented to HBBT+RPPSP. Outcomes included changes in the resuscitation practices, fresh stillbirths (FSB) and early neonatal deaths <1 week (ENND). RESULTS: There were 1350 and 3040 deliveries before and after HBBT+RPPSP, respectively, with no significant differences between the two cohorts regarding maternal age, education or area of birth. Drying of the newborn increased almost tenfold (8.4%, n=113 to 74.9%, n=1011) while suctioning of the mouth/nose decreased fivefold (80.3%, n=2442 to 14.4%, n=437) following HBBT+RPPSP. Pre-HBBT+RPPSP9/18 (50%) newborns who had mouth-to-mouth ventilation died, compared with 13/119 (11%) who received bag-mask ventilation post-HBBT+RPPSP. Excluding 11 macerated fetuses, there were 55 perinatal deaths: 14 FSB/18 ENND (6 months pre-HBBT+RPPSP) and 10 FSB/13 ENND (18 months post-HBBT+RPPSP). FSB rates decreased from 10.5 to 3.3 per 1000 births ((χ2)=8.6209, p=0.003), while ENND rates decreased from 13.5 to 4.3 per 1000 live births ((χ2)=10.9369, p=0.001) pre-HBBT+RPPSP and post-HBBT+RPPSP, respectively. CONCLUSION: In a selected group of VMWs, HBBT+RPPSP was associated with improvements in newborn resuscitation and perinatal outcomes. HBBT+RPPSP could have immense benefits if propagated nationally to all 17 000 VMWs in Sudan.

Osteitis of the radius following Bacillus Calmette-Guérin vaccination at birth: a case report.

BACKGROUND: The Bacillus Calmette-Guérin vaccine, which is used for the prevention of tuberculosis, is considered protective against the severe forms of childhood tuberculosis. However, some serious adverse reactions including osteitis of the long bones can occur. CASE PRESENTATION: We report a case of an 18-month-old Sudanese girl who presented at the age of 3 months with swelling of her left forearm following Bacillus Calmette-Guérin vaccination administered at birth. Radiological and histological investigations confirmed tuberculous osteitis of the distal radius. She responded very well to antituberculous treatment with complete healing at follow-up visits. To the best of our knowledge this is the first case report of osteitis of the radius following Bacillus Calmette-Guérin vaccination described from Sudan. CONCLUSIONS: Bacillus Calmette-Guérin osteitis, although rare, should be considered a possible complication of the Bacillus Calmette-Guérin vaccination, and early diagnosis and treatment are essential.

Brain tuberculoma, an unusual cause of stroke in a child with trisomy 21: a case report.

BACKGROUND: Tuberculosis remains a public health problem in developing countries and is associated with lethal central nervous system complications. Intracranial tuberculomas occur in 13% of children with neurotuberculosis. Patients with trisomy 21 have an increased risk for stroke, which usually stems from cardiovascular defects. CASE PRESENTATION: We report a case of a 12-year-old Sudanese boy with trisomy 21 who was presented to our hospital with focal convulsions and right-sided weakness. The results of neuroimaging and histopathological examinations were consistent with cerebral tuberculoma. The patient had a good initial response to antituberculosis drugs and steroids. To the best of our knowledge, this is the first case report of multiple brain tuberculomas described in a child with trisomy 21. CONCLUSIONS: Patients with trisomy 21 have an increased risk for stroke. Our patient had an exceptional case of stroke caused by tuberculoma. The present case emphasizes the need to consider tuberculomas in the differential diagnosis of children with neurological symptoms living in areas of high tuberculosis incidence.

Randomized Trials Comparing Inactivated Vaccine After Medium- or High-titer Measles Vaccine With Standard Titer Measles Vaccine After Inactivated Vaccine: A Meta-analysis.

BACKGROUND: Observational studies have suggested that girls have higher mortality if their most recent immunization is an inactivated vaccine rather than a live vaccine. We therefore reanalyzed 5 randomized trials of early measles vaccine (MV) in which it was possible to compare an inactivated vaccines [after medium-titer MV (MTMV) or high-titer MV (HTMV)] and a live standard titer MV (after an initial inactivated vaccine). METHODS: The trials were conducted in Sudan, Senegal, The Gambia and Guinea-Bissau. The intervention group received live MTMV or HTMV from 4 to 5 months and then an inactivated vaccine from 9 to 10 months of age; the control children received inactivated vaccine/placebo from 4 to 5 months and standard titer MV from 9 to 10 months of age. We compared mortality from 9 months until end of study at 3 to 5 years of age for children who received inactivated vaccine (after MTMV or HTMV) and standard titer MV (after inactivated vaccine), respectively. The original datasets were analyzed using a Cox proportional hazards model stratified by trial. RESULTS: The mortality rate ratio (MRR) was 1.38 (95% confidence interval: 1.05-1.83) after an inactivated vaccine (after MTMV or HTMV) compared with a standard titer MV (after inactivated vaccine). Girls had a MRR of 1.89 (1.27-2.80), whereas there was no effect for boys, the sex-differential effect being significant (P = 0.02). Excluding measles cases did not alter these conclusions, the MRR after inactivated vaccines (after MTMV or HTMV) being 1.40 (1.06-1.86) higher overall and 1.92 (1.29-2.86) for girls. Control for variations in national immunization schedules for other vaccines did not modify these results. CONCLUSIONS: After 9 months of age, all children had been immunized against measles, and mortality in girls was higher when they had received inactivated vaccines (after MTMV or HTMV) rather than live standard titer MV (after an inactivated vaccine).

Skills retention in Sudanese village midwives 1†year following Helping Babies Breathe training.

BACKGROUND: Over 80% of deliveries in Sudan occur in isolated villages, attended by village midwives (VMWs). Upgrading newborn resuscitation skills with the Helping Babies Breathe (HBB) programme could improve newborn survival rates. OBJECTIVE: To describe the competencies in newborn resuscitation of selected VMWs pre-HBB and post-HBB training. METHODS: In a prospective intervention study, the VMWs' performances in the HBB Objective Structured Clinical Examination B simulated scenario (manikin requiring face-mask ventilation (FMV)) were digitally recorded and analysed prior to and 3 and 12 months following HBB training. Regular manikin-based practice was encouraged following training. RESULTS: Pre-HBB training, 42% of 71 VMWs (of whom 61% were functionally illiterate) stimulated the non-breathing manikin by holding it by the legs and either stimulated/slapped (30.4%) or shook (12.7%) it, while 25% (18/71) provided manikin mouth-to-mouth ventilation. The low scorings on the 'preparation for birth' (0% and 3.1% at 3 and 12 months, respectively) were mainly due to failure to demonstrate the subitem of 'cleans hands'. The percentage of VMWs providing manikin FMV within the Golden Minute increased from 37.3% (25/67) to 72.3% (47/65) (p<0.005), but there were no significant differences in the number of VMWs producing at least five FMVs at 3 months (73%, 49/67) and 12 months (58%, 38/65), respectively. CONCLUSIONS: VMWs, despite a high illiteracy rate, absorbed and sustained HBB skills for at least a year. Regular, low intensity, manikin-based skills training with peers may have helped sustain FMV, but not hand-cleansing skills.

No evidence for short or long term morbidity after increased titer measles vaccination in Sudan.

BACKGROUND: Increased mortality rates have been reported after high titer measles [>10(5.0) plaque-forming units (PFU)] vaccination in several large studies in the developing world. An increased titer measles vaccine study conducted in Sudan included a prolonged prospective evaluation of childhood morbidity after vaccination. METHODS: Five hundred ten children (170 per group) were randomized to receive 1 of 3 regimens at 5 and 9 months of age: (1) meningococcal vaccine, then standard titer (50% tissue culture-infective dose, 103.8) Schwarz measles vaccine; (2) increased titer (10(4.7) PFU) Edmonston-Zagreb measles vaccine followed by meningococcal vaccine; and (3) increased titer (10(4.7) PFU) Connaught vaccine followed by standard titer Schwarz measles vaccine. RESULTS: Health workers collected information at 31,582 semi-monthly and monthly visits during 5 years. No increase in infant mortality was observed, but the statistical power was limited. There were 13, 13 and 10 deaths in the Schwarz, Edmonston-Zagreb and Connaught groups, respectively. There were no differences in duration or incidence of illness between groups at any time during the 5-year follow-up, with comparisons stratified by age and sex. Statistical power for each pairwise comparison was good, with at least 80% power to detect a difference of 1 day per month of illness and a 12% difference in the proportion of visits with an illness recorded. CONCLUSIONS: We were unable to document increased morbidity in recipients of the increased titer measles vaccines used in this study. These data do not support the hypothesis that increased mortality after increased titer vaccine exposure is the result of increased and cumulative morbidity.

Poor adherence to the World Health Organization guidelines of treatment of severe pneumonia in children at Khartoum, Sudan.

BACKGROUND: Community-acquired pneumonia (CAP) is as a major cause for childhood morbidity and mortality worldwide. This study was conducted to investigate the adherence and response of the WHO guidelines for treatment of severe pneumonia. METHOD: A cross-sectional study was conducted in the period of June 2009 to July 2010 at Khartoum Hospital, Sudan. Children admitted and treated for severe pneumonia were enrolled. RESULTS: Only 39 (18.8%) out of 208 enrolled children received prescriptions that were adherent to the WHO guidelines of treatment of severe pneumonia. In logistic regression none of the investigated variable (age, gender, and clinical presentations) was associated with the adherence to the WHO guidelines. There was no significant difference in the response between adherent and non-adherent prescriptions. There was no association between the demographic, clinical data, treatment-adherence to the guidelines and the patients' response. CONCLUSION: There is a poor (18.8%) adherence to the WHO guidelines of the treatment of severe pneumonia in the region regardless to the age, gender and clinical presentation.

Cystic fibrosis in Sudanese children: First report of 35 cases.

Cystic fibrosis is the most common severe genetic disorder among children of European descent. It is much less common in Africans and Asians. It affects most critically the lungs causing chronic lung disease, failure to thrive and social deprivation. This is a retrospective review of 35 Sudanese patients with confirmed cystic fibrosis. About 60% of cases presented before the age of 5 years and male to female ratio was 1.7:1.0. Consanguinity was reported in 25 of the families. The main presenting features were productive cough, wheeze and clubbing. The chest X-ray showed variable degrees of hyperinflation, collapse, cystic, fibrotic changes and bronchiectasis involving both upper and lower lobes with blurring of cardiac border and hilar vasculature in the majority of cases. The sweat chloride was between 70 and 140 mmol/l in 83% of the patients (positive > 60 mmol/l). Three patients underwent DNA study and confirmed to have cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. Gene study was not available for the rest of the patients. To our knowledge this is the first report of confirmed cases of cystic fibrosis in Sudanese patients.

Congenital cystic adenamatoid malformation: A case report.

We here report a rare case of congenital cystic adenamatoid malformation[CCAM]. This case presented early in the neonatal period with bilateral lung cysts and have favorable outcome. However, the patient continued to be oxygen dependent for more than six weeks.

Characteristics associated with severe pneumonia in under-five children admitted to emergency units of two teaching hospitals in Khartoum, Sudan.

Pneumonia, defined as infection of lung parenchyma, is associated with severe complications especially in the very young and old patients. It is the world's leading cause of childhood mortality. The World Health Organization (WHO) classification and guidelines are commonly used in Sudan in the diagnosis and management of pneumonia patients. A group of 224 patients at Gaafar Ibn Oaf Children's Hospital and Omdurman Children's Hospital were assessed and managed for severe presentation of pneumonia. The data collected showed that most of the patients were of low socioeconomic class families. The vast majority (99%) of patients had chronic exposure to tobacco smoke at home. Female patients (52.7%) were more than males, with 42% of the presenting patients in the less than 12 months age group. Pneumonia is a dangerous childhood menace that is associated with severe presentations. Public health community outreach programs should be put in place to raise awareness. The case fatality rate during the study period was 4%.

Treatment of severe malnutrition with 2-day intramuscular ceftriaxone vs 5-day amoxicillin.

BACKGROUND: Systemic antibiotics are routinely prescribed for severe acute malnutrition (SAM). However, there is no consensus regarding the most suitable regimen. In a therapeutic feeding centre in Khartoum, Sudan, a randomised, unblinded, superiority-controlled trial was conducted, comparing once daily intramuscular injection with ceftriaxone for 2 days with oral amoxicillin twice daily for 5 days in children aged 6-59 months with SAM. METHODS: Commencing with the first measured weight gain (WG) following admission, the risk difference and 95% confidence interval (95% CI) for children with a WG > or = 10 g/kg/day were calculated over a 14-day period. The recovery rate and case fatality ratio (CFR) between the two groups were also calculated. RESULTS: In an intention-to-treat analysis of 458 children, 53.5% (123/230) in the amoxicillin group and 55.7% (127/228, difference 2.2%, 95% CI -6.9-11.3) in the ceftriaxone group had a WG > or = 10 g/kg/day during a 14-day period. Recovery rate was 70% (161/230) in the amoxicillin group and 74.6% (170/228) in the ceftriaxone group (p=0.27). CFR was 3.9% (9/230) and 3.1% (7/228), respectively (p=0.67). Most deaths occurred within the 1st 2 weeks of admission. CONCLUSION: In the absence of severe complications, either ceftriaxone or amoxicillin is appropriate for malnourished children. However, in ambulatory programmes, especially where there are large numbers of admissions, ceftriaxone should facilitate the work of medical personnel.

Neonatal resuscitation courses for pediatric residents: comparison between Khartoum (Sudan) and Padova (Italy).

BACKGROUND: The efficacy of a Neonatal Resuscitation Program (NRP) has been previously evaluated in developed countries, but there is a lack of information regarding the impact of this teaching program in developing countries. Our aim was to compare the knowledge gained by University of Khartoum (Sudan) and University of Padova (Italy) pediatric residents following participation in the NRP course. METHODS: An 80-item questionnaire derived from the standard test contained in the American Heart Association and American Academy of Pediatrics Neonatal Resuscitation Manual was given to participants before and after the course. RESULTS: Twenty-five Sudanese and 26 Italian pediatric residents answered the pre- and postcourse questionnaire. The percentages of correct answers significantly improved from before to immediately after the course for both Sudanese (51.9 +/- 10.5% vs 84.9 +/- 5.8%; P < 0.01) and Italian (64.3 +/- 8.1% vs 94.0 +/- 3.9%; P < 0.01) pediatric residents. During the entire study, the scores obtained by Italian pediatric residents were higher than those reached by their Sudanese colleagues (P < 0.01). CONCLUSIONS: The trend of the knowledge attainment of both Sudanese and Italian pediatric residents was similar after NRP course participation. An NRP is effective in teaching neonatal resuscitation in developing countries.

The sequence of vaccinations and increased female mortality after high-titre measles vaccine: trials from rural Sudan and Kinshasa.

OBJECTIVE: West African studies have hypothesized that increased female mortality after high-titre measles vaccine (HTMV) was due to subsequent diphtheria-tetanus-pertussis (DTP) and inactivated polio vaccine (IPV) vaccinations. We tested two deductions from this hypothesis in HTMV studies from rural Sudan and Kinshasa; first, there should be no excess female mortality for HTMV recipients when DTP was not given after HTMV and second, excess female mortality should only be found among those children who received DTP after HTMV. STUDIES: The Sudanese trial randomised 510 children to Edmonston-Zagreb (EZ) HTMV, Connaught HTMV or a control vaccine (meningococcal). Both the Connaught HTMV and the control group received standard measles vaccine at 9 months. In the Kinshasa study 1023 children received one dose of HTMV at 6 months or two doses at 312 and 912 months of age. FINDINGS: First, the Sudan trial is one of the few randomised studies of measles vaccine; the EZ HTMV group had lower mortality between 5 and 9 months of age than controls, the mortality ratio (MR) being 0.00 (p = 0.030). This effect was not due to prevention of measles infection. Second, both studies provided evidence that HTMV per se was associated with low mortality. In a combined analysis comparing both HTMV groups with controls, the HTMV groups had a MR of 0.09 (0.01-0.71) between 5 and 9 months of age. In Kinshasa, the HTMV recipients who did not receive simultaneous DTP had an annual mortality rate of only 1.0% between 6 months and 3 years of age. Third, the female-male MR was related to subsequent DTP vaccinations. In Kinshasa, the female-male MR was only 0.40 (0.13-1.27) among the HTMV recipients who did not receive further doses of DTP. In Sudan, the female-male mortality ratio in the EZ group was 3.89 (95% CI 1.02-14.83) and the female-male MR increased with number of doses of DTP likely to have been given during follow-up (trend, p = 0.043). Fourth, in Kinshasa, mortality was higher among children who had received HTMV and DTP simultaneously than among children who had received HTMV alone (MR = 5.38 (1.37-21.2)). CONCLUSIONS: Measles vaccine is associated with non-specific beneficial effects. When not given with DTP, HTMV per se was associated with low mortality. Increased female mortality was not found among children who did not receive DTP after HTMV. Hence, our deductions were supported and the sequence or combination of vaccinations may have an effect on sex-specific mortality patterns in low-income countries.

The efficacy of artemether versus quinine in the treatment of cerebral malaria.

Cerebral malaria remains a major cause of childhood morbidity. Quinine is the drug of choice for which resistance is now emerging. A total of 77 children admitted to Khartoum Children Emergency Hospital who conform to WHO criteria of cerebral malaria were randomly allocated to receive either artemether (1.6 mg/kg body wt., repeated after 12 hrs and then daily for four days) or quinine (10 mg/kg body wt in 10 ml/kg body wt of 5% dextrose in 0.9% saline intravenously. Repeated every 8 hrs and changed to oral administration when the child was able to drink to finish seven days). Response to therapy was evaluated using fever clearance time (FCT), time of regaining consciousness (TRC) and parasite clearance time (PCT). The FCT (mean+SD), TRC and PCT for the artemether-treated group were 32 (+13) hrs, 21 (+11) hrs and 36 (+18) hrs, respectively, while for the quinine-treated group the respective figures were 36 (+18), 26 (+15) hrs and 41 (+12) hrs. The response to artemether was slightly better than that of quinine, but the differences between the two groups were not statistically significant. The outcome in terms of cure rate, neurological sequalae and case fatality was also comparable.

Introducing qualitative perinatal audit in a tertiary hospital in Sudan.

In a 3-month period, May to August 2000, the perinatal mortality rate at Omdurman Maternity Hospital (OMH), Sudan, was 8.2%. Two groups of perinatal deaths, intrapartum deaths of non-malformed infants and neonatal deaths of mature infants above 34 weeks, both considered to be potentially avoidable by improved care, were in excess when compared with other regions. It was therefore decided to perform in-depth assessment of cases in these two groups. An interdisciplinary internal audit was designed in collaboration with two external obstetricians. The audit activity was preceded by a 2-day workshop at the hospital. Individual assessments based on 43 detailed narratives were followed by regular consensus meetings. This structure seemed useful for interdisciplinary discussions, and the audit process resulted in several specific suggestions for quality improvement in data collection, interdisciplinary collaboration, and obstetric and neonatal care. The present audit activity is not very resource demanding and therefore a good starting point for quality assurance in a developing country. However, since adverse outcome audit only focuses on selected cases and may encourage interventions without considering the full impact on the population, it should not stand alone. Audit of perinatal deaths should be combined with other quantitative and qualitative quality assessment activities for improvement of perinatal care.