Calvarial hyperpigmentation.

Background: Osseous hyperpigmentation of the calvarium is an extremely rare finding with only few reported cases in literature. Case Description: The case is of a 59-year-old Caucasian male who presented with an acute history of generalized tonic clonic seizures and progressive weakness of the right upper limb. He had a background history of a malignant melanoma which had been resected from his left external acoustic meatus 4 weeks prior. Neuroimaging of the brain showed an intra-axial space-occupying lesion in his left parietal lobe with no associated osseous changes. A left mini parietal craniotomy was performed which revealed black discoloration of the parietal bone. The lesion was successfully resected and the bone flap was secured back in place. The patient was discharged on the 4th day postoperatively with no complications. The unusual finding of black discoloration of the calvarium was found to be secondary to adolescent tetracycline use. Conclusion: Calvarial hyperpigmentation is a phenomenon encountered incidentally and will often come as surprise for surgeons. Once encountered, thorough history taking and examination should be done to investigate the cause.

Single surgeon case series of myelomeningocele repairs in a developing world setting: Challenges and lessons.

Purpose: Neural Tube Defects are the second most common group of birth malformations following congenital heart anomalies, with myelomeningoceles being the most severe manifestation (MMC). They require expedited surgical repair, preferably within 72 â€‹h of birth. In low- and middle-income countries (LMIC) where resources are limited, timing to MMC repair is not optimal and leads to undesirable outcomes. The purpose of this study was to determine whether a proactive approach in a setting from a LMIC could achieve repair within 72 â€‹h. Methods: A concerted effort to expedite repair of all neonates referred with a MMC was undertaken from 01 January 2014 to 1 August 2015. A consensus was reached between neonatologists and neurosurgeons that neonates born or admitted with a MMC are referred immediately to surgeons and that repair will be performed within 72 â€‹h of birth. Hospital records of neonates who had MMC repaired during this period were reviewed for infant characteristics and hospital outcomes. Results: 24 patients with a MMC were operated upon by the senior author (CP) during the study period. Only 13 of these patients were born at the treating institution and 11 were referred from outside hospitals. Most MMCs were in the lumbosacral region and mean MMC surface area was 19.4 â€‹cm2. Mean time to repair for the entire series was 13.6 days. Patients born at the treating institution has a mean time to repair of 10.5 days and patients referred from outside had a mean time to repair of 17.3 days. Series wide, only 21% of neonates were operated upon in less than 72 â€‹h. Conclusion: Despite a pro-active commitment to repairing MMCs within 72 â€‹h for the duration of this series, satisfactory time to repair was not achieved. Late referral, referral from outside hospitals and operating theatre availability were the predominant factors leading to delay in MMC repair. Nevertheless, time to repair in our series was significantly shorter than that reported in MMC repair series based in similar environments. This suggests that even if the gold-standard of a 72-h window cannot be achieved, neonates benefit from much quicker repair when a concerted effort to minimise repair time is employed. This study also highlights the urgent need to address health care constraints in LMIC to improve outcomes for this vulnerable group.

Flexible endoscope-assisted suture release and barrel stave osteotomy for the correction of sagittal synostosis.

OBJECTIVE: Early suturectomy with a rigid endoscope followed by orthotic cranial helmet therapy is an accepted treatment option for single-suture craniosynostosis. To the authors' knowledge, flexible endoscope-assisted suture release (FEASR) has not been previously described. Presented herein is their experience with FEASR for the treatment of isolated sagittal craniosynostosis. METHODS: A retrospective analysis of the health records of patients who had undergone FEASR between March 2018 and December 2020 was performed. Patients under the age of 6 months who had been diagnosed with isolated sagittal synostosis were considered eligible for FEASR. Exclusion criteria included syndromic synostosis or multiple-suture synostosis. The cephalic index, the primary measure of the cosmetic endpoint, was calculated at prespecified intervals: immediately preoperatively and 6 weeks and 12 months postoperatively. Parental satisfaction with the cosmetic outcome was determined throughout the clinical follow-up and documented according to a structured questionnaire for the first 12 months. RESULTS: A total of 18 consecutive patients met the criteria for study inclusion. The mean patient age at the time of surgery was 3.4 months (range 2-6 months). All patients underwent a wide craniectomy with no need to convert to an open procedure. The mean craniectomy width was 3.61 cm. Estimated blood loss ranged from 5 to 30 ml. The mean operative time was 75 minutes. No intraoperative complications were observed. The average length of stay was 2.6 days. The mean cephalic index was 67.7 preoperatively, 77.1 at 6 weeks postoperatively, and 76.3 at 1 year postoperatively. The mean percentage change in the cephalic index from preoperatively to the 12-month follow-up was 10.44 (p < 0.001). The mean follow-up was 17 months (range 12-28 months). All parents were satisfied with the cosmetic outcome of the procedure. No patients developed symptoms of raised intracranial pressure (ICP) or needed invasive ICP monitoring during the follow-up period. No patients required reoperation. CONCLUSIONS: In this modest single-hospital series, the authors demonstrated the feasibility of FEASR in treating sagittal synostosis with favorable cosmetic outcomes. The morbidity profile and resource utilization of the procedure appear similar to those of procedures conducted via traditional rigid endoscopy.

Keyhole Approaches Applied to Clipping of Acutely Ruptured Intracerebral Aneurysms-A Technical Note and Case Series.

BACKGROUND: Evolution of keyhole techniques in aneurysm surgery allows for definitive surgical management of aneurysmal pathology with little disruption of normal surrounding tissue. While experienced vascular neurosurgeons are increasingly applying keyhole techniques to unruptured aneurysms, experience with ruptured aneurysms is limited. OBJECTIVE: We sought to explore technical nuances and present operative outcomes for our series of 40 consecutive patients presenting with ruptured intracerebral aneurysms treated with surgical clipping via a keyhole approach. METHODS: This study is a consecutive, single-surgeon, single-center retrospective case series of aneurysms clipped with keyhole approaches at Helen Joseph Hospital in Johannesburg, South Africa. Patients presenting with subarachnoid hemorrhage were worked up exclusively with computed tomography. On the basis of vessel location and unique anatomic features, aneurysms were clipped through one of these approaches: minipterional, supraorbital, or keyhole interhemispheric. Operative details were assessed on retrospective file review, and patient outcomes were assessed on clinic follow-up. RESULTS: A minipterional approach was used for 55% of cases, the supraorbital approach in 30% of cases, and the mini-interhemispheric approach in 15% of cases. The intraoperative aneurysm rupture rate was 26.2%. Complete aneurysm occlusion was achieved in 97.4% with none of the 40 cases requiring conversion of a keyhole to a larger craniotomy. A good outcome was achieved for 72.5% of patients (modified Rankin Scale score ≤2). For patients presenting with World Federation of Neurological Surgeons grade I to III subarachnoid hemorrhage, 92.9% achieved a good outcome. CONCLUSIONS: The present series supports the concept that sound technical execution of keyhole approaches, even in the setting of acutely ruptured cerebral aneurysms, is a viable option for clipping of intracranial aneurysms.

Ruptured presentation of superficial temporal artery pseudoaneurysm treated with anastomotic repair: Case report.

Superficial temporal artery (STA) pseudoaneurysm is a very rare occurrence that usually presents as a pulsatile mass along the STA distribution following trauma or an iatrogenic cause. We report a case of STA pseudoaneurysm that developed in a 32 year old male following blunt trauma. Unfortunately, the pseudoaneurysm was missed and led to multiple hospital presentations that culminated in an acute bleeding episode. Surgical resection of the pseudoaneurysm was performed and the STA was reconstructed with an STA-STA anastomosis. To our knowledge, this is the second reported case of an STA pseudoaneurysm treated with an STA-STA anastomosis. This case report aims to bring awareness. Although extremely rare, the importance of treating the presence of a pulsatile mass along the STA distribution following a history of trauma or recent cranial surgery with a high level of suspicion is imperative.

Supraorbital eyebrow approach: A single-center experience.

Background: Keyhole neurosurgery is the notion of safely removing brain and skull base lesions through smaller and more precise openings that lessen collateral damage to the surrounding scalp, brain, blood vessels, and nerves. The traditional frontal and pterional approaches require large craniotomies and this predisposes patients to significant and avoidable morbidity. With the growing expectation for minimally invasive surgery, we present our experience with the supraorbital keyhole craniotomy for surgical lesions in the anterior cranial fossa and parasellar regions. Methods: We retrospectively analyzed and evaluated all cases of neoplastic, vascular, trauma, and infective pathologies of the anterior fossa and parasellar regions treated using a keyhole approach, the supraorbital eyebrow (SOE) approach from January 2018 to June 2022. Treatment outcomes were evaluated based on pathology. Results: A total of 50 patients underwent a SOE craniotomy during the study period (28 females and 22 males). Their average age ranged from 12 to 86 years, with a mean age of 47.4 years. All patients had anterior skull base and/or anterior frontal lobe pathologies: (23 tumors, 17 ruptured aneurysms, five traumatic frontal hematomas, three extradural empyema, one cerebral cavernous malformation, and one traumatic frontal skull base fracture with dural tear and CSF leak). Gross total tumor resection was achieved in 87% of cases (13 meningiomas of which six were giant, three gliomas, two craniopharyngiomas, and two cerebral metastases). Clip ligation occlusion rate for our aneurysm cases was 100% and intraoperative rerupture was observed in three cases. Mean ICU stay was 2.2 days for the entire series. The overall 30-day mortality rate for our series was 16% (eight deaths). This was highest in the ruptured aneurysm subgroup, with all 5 mortality cases in the aneurysmal subgroup presenting as World Federation of Neurological Surgeons (WFNS) grades ≥ III. 4 of the deaths were in WFNS IV and V patients. The most frequent perioperative complication was transient periorbital swelling which resolved within 7 days. It was observed in 18 of the 50 patients. The next common complications in descending frequency were eyebrow alopecia (three cases), supraorbital hypoesthesia (two cases), CSF leak (two cases), and surgical site infection (one case). There was one approach-related intraoperative complication secondary to carotid injury in a giant meningioma redo case. Conversion to a larger craniotomy was never necessary. Clinical outcome for our cases was evaluated according to the Modified Rankin Scale (mRS) at 3-month postsurgery. A good clinical outcome (mRS ≤ 2) was achieved for 78% of our patients. Conclusion: The SOE approach craniotomy is an effective minimally invasive approach for various pathologies of the anterior cranial base and parasellar regions. With experience, giant tumors and complex vascular pathology can be addressed with this keyhole approach.

Primary empty sella syndrome associated with visual deterioration salvaged by chiasmapexy: Report of a case and discussion of the literature.

BACKGROUND: Empty sella syndrome (ESS) is a condition in which there is loss of volume of the pituitary gland, which is the normal constituent of the sella turcica. There may be visual and endocrine deficits associated with this condition, and radiologically, there may be downward prolapse of the optic chiasm. It occurs in a primary ESS, poorly understood form, as well as a secondary ESS form that follows medical or surgical treatment of a pituitary macroadenoma, or else spontaneous hemorrhage into such a tumor. CASE DESCRIPTION: A 56-year-old man presenting with deficits of both visual acuity and visual fields in the setting of radiological ESS without associated optic chiasm prolapse is discussed. He underwent endoscopic endonasal chiasmapexy with gradual improvement of his visual function over the following 6 months. CONCLUSION: ESS is a potentially potent cause of visual deterioration that lends itself to reversal through a relatively simple neurosurgical technique. This case illustrates that actual prolapse of the chiasm is neither a prerequisite for visual deterioration nor its reversal the mechanism of visual improvement after chiasmapexy, raising the question of the mechanisms at play in cases such as this. It confirms the role of chiasmapexy in the management of selected cases of ESS.

Acalvaria - report of a case and discussion of the literature.

Acalvaria is a rare condition indeed, defined as the absence of the flat bones of the skull, as well as the associated muscles and dura, with, in some cases, normal skull base bones and normal brain structures. It has been reported as a fatal congenital condition, because of the failure of afflicted children to survive for extended periods. There have, however, been reports of extended survival. The first report of this condition was in 1996, involving an 11-year-old child who had severe mental retardation. Since then, there have been few further reports of this condition, generally in infants.

First Report of Renal Cell Carcinoma Metastasizing to the Clivus in a Pediatric Patient.

BACKGROUND: The clivus is a rare site of tumor occurrence in general, and metastases to this site are especially rare. Renal cell carcinoma is an uncommon entity in the pediatric population. Although not infrequent in adults, when it does occur, metastases to the clivus are extremely uncommon, only having been reported 3 times in the literature. All of these cases involved adults in their sixth decade. CASE DESCRIPTION: We present the first report in the literature of renal cell carcinoma occurring in a pediatric patient and spreading to the clivus. This 11-year-old girl presented with headaches and diplopia based on a left-sided sixth cranial nerve palsy, in the context of a wasting disease. She was also found to have vague abdominal fullness, although it was only after biopsy of a clivus lesion identified on brain scanning that its true nature became apparent, prompting abdominal scans, which revealed a renal mass with hepatic metastases. CONCLUSIONS: This article reports for the first time in the literature the spread of a translocation renal cell carcinoma to the clivus in a young child. This serves to alert practitioners to this possibility when faced with a similar scenario.

Demographic profile of patients diagnosed with intracranial meningiomas in two academic hospitals in Johannesburg, South Africa: a 12-month prospective study.

BACKGROUND: Meningiomas are common brain tumours and display gender, racial and ethnic differences in their demographic profile. The demographic profile of our patients diagnosed with intracranial meningiomas is presented and compared with the literature. OBJECTIVES: To determine the age, gender, racial and ethnic distribution of our patients diagnosed with intracranial meningiomas. METHODS: Consecutive patients (48 in number) seen at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) and Chris Hani Baragwanath Academic Hospital (CHBAH), Johannesburg, with histologically proven meningiomas over a 12 month period were recruited for the study. RESULTS: Meningiomas accounted for 33.8% of all primary brain tumours. The mean age of patients was 45.7 ± 10.5 years with a female-to-male ratio of 3.8:1. The mean age for male patients was 39.3 ± 13.5 years while that of female patients was 47.4 ± 9.0 years. The peak age range at presentation was in the fifth (41.7%) decade. The highest frequency was among Black Africans (75%) and Sotho ethnic nationality (27.1%). CONCLUSION: The study showed a female preponderance for intracranial meningiomas among our patients. Although intracranial meningiomas were more in frequency among Black Africans, the racial distribution mirrored our population distribution while the highest frequency was among Sotho ethnic nationality.

Long term study on the effect of mollusciciding with niclosamide in stream habitats on the transmission of schistosomiasis mansoni after community-based chemotherapy in Makueni District, Kenya.

BACKGROUND: Schistosoma mansoni infection is a persistent public health problem in many Kenyan communities. Although praziquantel is available, re-infection after chemotherapy treatment is inevitable, especially among children. Chemotherapy followed by intermittent mollusciciding of habitats of Biomphalaria pfeifferi, the intermediate host snail, may have longer term benefits, especially if timed to coincide with natural fluctuations in snail populations. METHODS: In this cohort study, the Kambu River (Intervention area) was molluscicided intermittently for 4 years, after mass chemotherapy with praziquantel in the adjacent community of Darajani in January 1997. The nearby Thange River was selected as a control (Non-intervention area), and its adjacent community of Ulilinzi was treated with praziquantel in December 1996. Snail numbers were recorded monthly at 9-10 sites along each river, while rainfall data were collected monthly, and annual parasitological surveys were undertaken in each village. The mollusciciding protocol was adapted to local conditions, and simplified to improve prospects for widespread application. RESULTS: After the initial reduction in prevalence attributable to chemotherapy, there was a gradual increase in the prevalence and intensity of infection in the non-intervention area, and significantly lower levels of re-infection amongst inhabitants of the intervention area. Incidence ratio between areas adjusted for age and gender at the first follow-up survey, 5 weeks after treatment in the non-intervention area and 4 months after treatment in the intervention area was not significant (few people turned positive), while during the following 4 annual surveys these ratios were 0.58 (0.39-0.85), 0.33 (0.18-0.60), 0.14 (0.09-0.21) and 0.45 (0.26-0.75), respectively. Snail numbers were consistently low in the intervention area as a result of the mollusciciding. Following termination of the mollusciciding at the end of 2000, snail populations and infections in snails increased again in the intervention area. CONCLUSION: The results of this study demonstrate that in the Kenyan setting a combination of chemotherapy followed by intermittent mollusciciding can have longer term benefits than chemotherapy alone.

Anopheles gambiae and Anopheles arabiensis population densities and infectivity in Kopere village, Western Kenya.

INTRODUCTION: This study was conducted in a sugar belt region of western Kenya interfacing epidemic and endemic malaria transmission. We investigated Anopheles gambiae sensu stricto (ss) and Anopheles arabiensis species compositions and densities, human host choice, and infectivity. METHODOLOGY: Mosquitoes were captured using pyrethrum spray catch technique and first identified based on morphology; species were confirmed by PCR. Blood meal preference and sporozoite rates were determined by ELISA. Parity rates and entomological inoculation rates (EIR) were determined. Seasonal densities were compared against environmental temperatures, relative humidity and rainfall. RESULTS: In total 2,426 An. gambiae were collected.  Out of 1,687 female blood-fed mosquitoes, 272 were randomly selected for entomological tests. An. gambiae ss and An. arabiensis comprised 75% (205/272) and 25% (68/272) of the selection, respectively. An. gambiae ss had higher preference for human blood (97%; n=263/272) compared with An. arabiensis, which mostly fed on bovines (88%; n=239/272).  The sporozoite and parity rates were 6% (16/272) and 66% (179/272) for An. gambiae ss and 2% (4/272) and 53% (144/272) for An. arabiensis respectively, while EIR was 0.78 infective bites/person/night.  Climate (ANOVA; F=14.2; DF=23) and temperature alone (r=0.626; t=3.75; p=0.001) were significantly correlated with vector densities. CONCLUSION: An. gambiae ss are the most efficient malaria vector mosquito species in Kopere village. Because An. gambiae ss largely rests and feeds indoors, use of indoor residual spray and insecticide-treated nets is likely the most suitable approach to malaria vector control in Kopere village and other parts of Kenya where this species is abundant. 

Analysis of complex patterns of human exposure and immunity to Schistosomiasis mansoni: the influence of age, sex, ethnicity and IgE.

BACKGROUND: Numerous factors may influence Schistosoma infection intensity and prevalence within endemic communities, including exposure-related factors such as local environment and behaviour, and factors relating to susceptibility to infection such as immunology and genetics. While animal studies performed in the laboratory can be tightly controlled, human populations are highly heterogeneous, varying according to demographic characteristics, genetic background and exposure to infection. The heterogeneous nature of human water contact behaviour in particular makes it difficult to distinguish between a lack of cercarial exposure and reduced susceptibility to infection as the cause for low levels of infection in the field. METHODS AND PRINCIPAL FINDINGS: In this study we investigate risk factors for Schistosoma mansoni infection in a rural Ugandan fishing community receiving treatment as part of a multi-disciplinary longitudinal reinfection study. More specifically, we examine the influence that age, sex and ethnic background have on susceptibility to reinfection after anti-helminth drug treatment, but use individual estimates of cercarial exposure and multivariable methods in an attempt to remove noise created by environmental and behavioural heterogeneities. We then investigate whether schistosome-specific IgE immune responses could account for any remaining variations in susceptibility to reinfection. Our findings suggest that observed ethnic- and sex-related variations in S. mansoni reinfection were due to variations in cercarial exposure, as opposed to biological differences in susceptibility to infection. Age-related differences in reinfection were not explained by exposure, however, and appeared linked to the balance of IgE and IgG(4) to the tegumental antigen SmTAL1 (formerly Sm22.6), which itself was significantly related to resistance to reinfection. CONCLUSIONS: This study highlights the benefit of taking a multidisciplinary approach in complex field settings; it allows the ecology of a population to be understood and thus more robust conclusions to be made.

Locating irregularly shaped clusters of infection intensity.

Patterns of disease may take on irregular geographic shapes, especially when features of the physical environment influence risk. Identifying these patterns can be important for planning, and also identifying new environmental or social factors associated with high or low risk of illness. Until recently, cluster detection methods were limited in their ability to detect irregular spatial patterns, and limited to finding clusters that were roughly circular in shape. This approach has less power to detect irregularly-shaped, yet important spatial anomalies, particularly at high spatial resolutions. We employ a new method of finding irregularly-shaped spatial clusters at micro-geographical scales using both simulated and real data on Schistosoma mansoni and hookworm infection intensities. This method, which we refer to as the "greedy growth scan", is a modification of the spatial scan method for cluster detection. Real data are based on samples of hookworm and S. mansoni from Kitengei, Makueni district, Kenya. Our analysis of simulated data shows how methods able to find irregular shapes are more likely to identify clusters along rivers than methods constrained to fixed geometries. Our analysis of infection intensity identifies two small areas within the study region in which infection intensity is elevated, possibly due to local features of the physical or social environment. Collectively, our results show that the "greedy growth scan" is a suitable method for exploratory geographical analysis of infection intensity data when irregular shapes are suspected, especially at micro-geographical scales.

Health implications of chronic hepatosplenomegaly in Kenyan school-aged children chronically exposed to malarial infections and Schistosoma mansoni.

Hepatosplenomegaly among school-aged children in sub-Saharan Africa is highly prevalent. Two of the more common aetiological agents of hepatosplenomegaly, namely chronic exposure to malaria and Schistosoma mansoni infection, can result in similar clinical presentation, with the liver and spleen being chronically enlarged and of a firm consistency. Where co-endemic, the two parasites are thought to synergistically exacerbate hepatosplenomegaly. Here, two potential health consequences, i.e. dilation of the portal vein (indicative of increased portal pressure) and stunting of growth, were investigated in a study area where children were chronically exposed to malaria throughout while S. mansoni transmission was geographically restricted. Hepatosplenomegaly was associated with increased portal vein diameters, with enlargement of the spleen rather than the liver being more closely associated with dilation. Dilation of the portal vein was exacerbated by S. mansoni infection in an intensity-dependent manner. The prevalence of growth stunting was not associated with either relative exposure rates to malarial infection or with S. mansoni infection status but was significantly associated with hepatosplenomegaly. Children who presented with hepatosplenomegaly had the lowest height-for-age Z-scores. This study shows that hepatosplenomegaly associated with chronic exposure to malaria and schistosomiasis is not a benign symptom amongst school-aged children but has potential long-term health consequences.

Urinary soluble egg antigen levels in Schistosoma haematobium infection in relation to sex and age of Kenyan schoolchildren following praziquantel treatment.

Schistosoma haematobium soluble egg antigen (SEA) secreted in urine can be assayed to determine egg tissue load and hence morbidity in infected individuals. A cohort of 158 infected children aged 4-18 years was followed-up for 33 days pre and post treatment with a single dose of praziquantel. There was a significant difference in the prevalence of S. haematobium between males and females (P < 0.05). There were also significant differences in egg counts between age group < or = 5 years compared with 6-8 years, 9-11 years and 12-14 years, and age group > or = 15 years compared with 6-8 years, 9-11 years and 12-14 years (P < 0.05). Comparison of SEA among age groups indicated a significant difference between age group < or = 5 years compared with 9-11 years, 12-14 years and > or = 15 years, and age group > or = 15 years compared with 9-11 years and 12-14 years (P < 0.05). There was a statistically significant correlation between levels of SEA and egg output (r2=0.961, P=0.010). These results are useful in the development of a SEA-based dipstick assay for field diagnosis of urinary schistosomiasis.

Can prenatal malaria exposure produce an immune tolerant phenotype? A prospective birth cohort study in Kenya.

BACKGROUND: Malaria in pregnancy can expose the fetus to malaria-infected erythrocytes or their soluble products, thereby stimulating T and B cell immune responses to malaria blood stage antigens. We hypothesized that fetal immune priming, or malaria exposure in the absence of priming (putative tolerance), affects the child's susceptibility to subsequent malaria infections. METHODS AND FINDINGS: We conducted a prospective birth cohort study of 586 newborns residing in a malaria-holoendemic area of Kenya who were examined biannually to age 3 years for malaria infection, and whose malaria-specific cellular and humoral immune responses were assessed. Newborns were classified as (i) sensitized (and thus exposed), as demonstrated by IFNgamma, IL-2, IL-13, and/or IL-5 production by cord blood mononuclear cells (CBMCs) to malaria blood stage antigens, indicative of in utero priming (n = 246), (ii) exposed not sensitized (mother Plasmodium falciparum [Pf]+ and no CBMC production of IFNgamma, IL-2, IL-13, and/or IL-5, n = 120), or (iii) not exposed (mother Pf-, no CBMC reactivity, n = 220). Exposed not sensitized children had evidence for prenatal immune experience demonstrated by increased IL-10 production and partial reversal of malaria antigen-specific hyporesponsiveness with IL-2+IL-15, indicative of immune tolerance. Relative risk data showed that the putatively tolerant children had a 1.61 (95% confidence interval [CI] 1.10-2.43; p = 0.024) and 1.34 (95% CI 0.95-1.87; p = 0.097) greater risk for malaria infection based on light microscopy (LM) or PCR diagnosis, respectively, compared to the not-exposed group, and a 1.41 (95%CI 0.97-2.07, p = 0.074) and 1.39 (95%CI 0.99-2.07, p = 0.053) greater risk of infection based on LM or PCR diagnosis, respectively, compared to the sensitized group. Putatively tolerant children had an average of 0.5 g/dl lower hemoglobin levels (p = 0.01) compared to the other two groups. Exposed not sensitized children also had 2- to 3-fold lower frequency of malaria antigen-driven IFNgamma and/or IL-2 production (p<0.001) and higher IL-10 release (p<0.001) at 6-month follow-ups, when compared to sensitized and not-exposed children. Malaria blood stage-specific IgG antibody levels were similar among the three groups. CONCLUSIONS: These results show that a subset of children exposed to malaria in utero acquire a tolerant phenotype to blood-stage antigens that persists into childhood and is associated with an increased susceptibility to malaria infection and anemia. This finding could have important implications for malaria vaccination of children residing in endemic areas.

Hepatosplenomegaly is associated with low regulatory and Th2 responses to schistosome antigens in childhood schistosomiasis and malaria coinfection.

Hepatosplenomegaly among Kenyan schoolchildren has been shown to be exacerbated where there is transmission of both Schistosoma mansoni and Plasmodium falciparum. This highly prevalent and chronic morbidity often occurs in the absence of ultrasound-detectable periportal fibrosis and may be due to immunological inflammation. For a cohort of school-age children, whole-blood cultures were stimulated with S. mansoni soluble egg antigen (SEA) or soluble worm antigen (SWA). Responses to SWA were found to be predominantly Th2 cytokines; however, they were not significantly associated with either hepatosplenomegaly or infection with S. mansoni or P. falciparum. In comparison, SEA-specific Th2 cytokine responses were low, and the levels were negatively correlated with S. mansoni infection intensities and were lower among children who were coinfected with P. falciparum. Tumor necrosis factor alpha levels in response to stimulation with SEA were high, and a negative association between presentation with hepatomegaly and the levels of the regulatory cytokines interleukin-6 and transforming growth factor beta(1) suggests that a possible mechanism for childhood hepatomegaly in areas where both malaria and schistosomiasis are endemic is poor regulation of an inflammatory response to schistosome eggs.

Hepatosplenomegaly in Kenyan schoolchildren: exacerbation by concurrent chronic exposure to malaria and Schistosoma mansoni infection.

OBJECTIVES: Chronic exposure to malaria exacerbates Schistosoma mansoni-associated hepatosplenomegaly in school-aged children. However, residual hepatosplenomegaly after treatment of S. mansoni with concurrent mollusciciding suggests malaria could be an underlying cause of hepatosplenomegaly. We investigated the role of chronic malaria in childhood hepatosplenomegaly in the presence and absence of concurrent S. mansoni infection. METHODS: Cross-sectional study of children in an study area where transmission of S. mansoni, but not malaria, is restricted to the eastern end. Clinical and ultrasound examinations were conducted, and parasitological and serological tests used to determine S. mansoni infection intensities and comparative exposure levels to malaria. RESULTS: Chronic exposure to malaria, as determined by Pfs-IgG3 levels, was associated with hepatosplenomegaly even in the absence of S. mansoni infection. Children infected with S. mansoni mostly had light to moderate infection intensities but greater enlargement of the liver and spleen than children who did not have schistosomiasis, and for the left liver lobe this was S. mansoni infection intensity dependent. CONCLUSIONS: Children chronically exposed to malaria but without S. mansoni infection can have hepatosplenomegaly, which even light S. mansoni infections can exacerbate in an intensity-dependent manner. Thus, concurrent chronic exposure to S. mansoni and Plasmodium falciparum can have an additive or synergistic effect on childhood morbidity.

Age-adjusted Plasmodium falciparum antibody levels in school-aged children are a stable marker of microgeographical variations in exposure to Plasmodium infection.

BACKGROUND: Amongst school-aged children living in malaria endemic areas, chronic morbidity and exacerbation of morbidity associated with other infections are often not coincident with the presence or levels of Plasmodium parasitaemia, but may result from long-term exposure to the parasite. Studies of hepatosplenomegaly associated with Schistosoma mansoni infection and exposure to Plasmodium infection indicate that differences that occur over 1-2 km in levels of Plasmodium transmission are related to the degree of exacerbation of hepatosplenomegaly and that Plasmodium falciparum schizont antigen (Pfs)-IgG3 levels may be a marker for the differing levels of exposure. METHODS: To investigate the validity of Pfs-IgG3 measurements as a tool to assess these comparative exposure levels on a microgeographical scale, cross-sectional community surveys were conducted over a 10 x 6 km study site in Makueni District, Kenya, during low and high malaria transmission seasons. During both high and low malaria transmission seasons, thick blood smears were examined microscopically and circulating Pfs-IgG3 levels measured from dried blood spot elute. GIS techniques were used to map prevalence of parasitaemia and Pfs-IgG3 levels. RESULTS: Microgeographical variations in prevalence of parasitaemia were observed during the high but not the low transmission season. Pfs-IgG3 levels were stable between high and low transmission seasons, but increased with age throughout childhood before reaching a plateau in adults. Adjusting Pfs-IgG3 levels of school-aged children for age prior to mapping resulted in spatial patterns that reflected the microgeographical variations observed for high season prevalence of parasitaemia, however, Pfs-IgG3 levels of adults did not. The distances over which age-adjusted Pfs-IgG3 of school-aged children fluctuated were comparable with those distances over which chronic morbidity has previous been shown to vary. CONCLUSION: Age-adjusted Pfs-IgG3 levels of school-aged children are stable and when mapped can provide a tool sensitive enough to detect microgeographical variations in malaria exposure, that would be useful for studying the aetiology of morbidities associated with long-term exposure and co-infections.