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2.  Safety of Seasonal Malaria Chemoprevention (SMC) with Sulfadoxine-Pyrimethamine plus Amodiaquine when Delivered to Children under 10 Years of Age by District Health Services in Senegal: Results from a Stepped-Wedge Cluster Randomized Trial 
PLoS ONE  2016;11(10):e0162563.
It is recommended that children aged 3 months to five years of age living in areas of seasonal transmission in the sub-Sahel should receive Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) during the malaria transmission season. The purpose of this study was to evaluate the safety of SMC with SPAQ in children when delivered by community health workers in three districts in Senegal where SMC was introduced over three years, in children from 3 months of age to five years of age in the first year, then in children up to 10 years of age.
A surveillance system was established to record all deaths and all malaria cases diagnosed at health facilities and a pharmacovigilance system was established to detect adverse drug reactions. Health posts were randomized to introduce SMC in a stepped wedge design. SMC with SPAQ was administered once per month from September to November, by nine health-posts in 2008, by 27 in 2009 and by 45 in 2010.
After three years, 780,000 documented courses of SMC had been administered. High coverage was achieved. No serious adverse events attributable to the intervention were detected, despite a high level of surveillance.
SMC is being implemented in countries of the sub-Sahel for children under 5 years of age, but in some areas the age distribution of cases of malaria may justify extending this age limit, as has been done in Senegal. Our results show that SMC is well tolerated in children under five and in older children. However, pharmacovigilance should be maintained where SMC is implemented and provision for strengthening national pharmacovigilance systems should be included in plans for SMC implementation.
Trial Registration NCT 00712374
PMCID: PMC5072628  PMID: 27764102
3.  Childhood pneumonia and crowding, bed-sharing and nutrition: a case-control study from The Gambia 
SETTING: Greater Banjul and Upper River Regions, The Gambia.
OBJECTIVE: To investigate tractable social, environmental and nutritional risk factors for childhood pneumonia.
DESIGN: A case-control study examining the association of crowding, household air pollution (HAP) and nutritional factors with pneumonia was undertaken in children aged 2–59 months: 458 children with severe pneumonia, defined according to the modified WHO criteria, were compared with 322 children with non-severe pneumonia, and these groups were compared to 801 neighbourhood controls. Controls were matched by age, sex, area and season.
RESULTS: Strong evidence was found of an association between bed-sharing with someone with a cough and severe pneumonia (adjusted OR [aOR] 5.1, 95%CI 3.2–8.2, P < 0.001) and non-severe pneumonia (aOR 7.3, 95%CI 4.1–13.1, P < 0.001), with 18% of severe cases estimated to be attributable to this risk factor. Malnutrition and pneumonia had clear evidence of association, which was strongest between severe malnutrition and severe pneumonia (aOR 8.7, 95%CI 4.2–17.8, P < 0.001). No association was found between pneumonia and individual carbon monoxide exposure as a measure of HAP.
CONCLUSION: Bed-sharing with someone with a cough is an important risk factor for severe pneumonia, and potentially tractable to intervention, while malnutrition remains an important tractable determinant.
PMCID: PMC5019143  PMID: 27725055
Africa; risk factors; cough; household air pollution; particulate matter
4.  Effect of Age and Vaccination With a Pneumococcal Conjugate Vaccine on the Density of Pneumococcal Nasopharyngeal Carriage 
This study evaluated the impact of age and pneumococcal vaccination on the density of pneumococcal nasopharyngeal carriage. Among colonized individuals, density decreased with increasing age. Time-trends analysis revealed that pneumococcal vaccination appeared to lower the density of nasopharyngeal carriage.
Background. This study evaluated the impact of age and pneumococcal vaccination on the density of pneumococcal nasopharyngeal carriage.
Methods. A cluster-randomized trial was conducted in rural Gambia. In 11 villages (the vaccine group), all residents received 7-valent pneumococcal conjugate vaccine (PCV-7), while in another 10 villages (the control group), only children <30 months old or born during the study period received PCV-7. Cross-sectional surveys (CSSs) were conducted to collect nasopharyngeal swabs before vaccination (baseline CSS) and 4, 12, and 22 months after vaccination. Pneumococcal density was defined using a semiquantitative classification (range, 1–4) among colonized individuals. An age-trend analysis of density was conducted using data from the baseline CSS. Mean pneumococcal density was compared in CSSs conducted before and after vaccination.
Results. Mean bacterial density among colonized individuals in the baseline CSS was 2.57 for vaccine-type (VT) and non–vaccine-type (NVT) pneumococci; it decreased with age (P < .001 for VT and NVT). There was a decrease in the density of VT carriage following vaccination in individuals older than 5 years (from 2.44 to 1.88; P = .001) and in younger individuals (from 2.57 to 2.11; P = .070) in the vaccinated villages. Similar decreases in density were observed with NVT within vaccinated and control villages. No significant differences were found between vaccinated and control villages in the postvaccination comparisons for either VT or NVT.
Conclusions. A high density of carriage among young subjects might partly explain why children are more efficient than adults in pneumococcal transmission. PCV-7 vaccination lowered the density of VT and of NVT pneumococcal carriage in the before-after vaccination analysis.
Clinical Trials Registration. ISRCTN51695599.
PMCID: PMC3423933  PMID: 22700830
5.  Trial of Chloramphenicol for Meningitis in Northern Savanna of Africa 
British Medical Journal  1973;3(5876):379-381.
In a controlled trial chloramphenicol proved as effective and much cheaper than penicillin for the treatment of group A meningococcal meningitis in Zaria, Nigeria. A short course of five days cured most patients. Adults and older children were soon able to take chloramphenicol by mouth, which reduced the cost and simplified treatment.
It is suggested that chloramphenicol is a suitable alternative to sulphonamides for the treatment of meningococcal meningitis in those parts of Africa where the organism is sulphonamide-resistant.
PMCID: PMC1586699  PMID: 4199744
6.  Pneumococcal antigen in lobar pneumonia. 
Journal of Clinical Pathology  1975;28(2):118-123.
This paper describes the value in diagnosis and the clinical implications of the detection of pneumococcal antigen in patients with lobar pneumonia. Ninety-eight patients with lobar pneumonia were investigated. Pneumococcal antigen was detected by counter-current immunoelectrophoresis in the sputum of 79% of patients with purulent sputum, in the serum of 29% of the patients, and in the urine of 54% of the patients. The diagnostic value of counter-current immunoelectrophoresis was not affected by prior antibiotic therapy. Patients with antigenaemia had a higher incidence of complications than those without as shown by an association between antigenaemia and jaundice, diarrhoea, and persistent pyrexia. Antigen persisted in the circulation for at least seven days in half the patients studied, possibly indicating the development of immunological tolerance to the polysaccharide antigen.
PMCID: PMC475610  PMID: 236330
7.  Allergic Complications of Meningococcal Disease I—Clinical Aspects 
British Medical Journal  1973;2(5869):733-737.
Out of 717 patients with meningococcal disease 53 showed one or more of the three allergic complications: 47 (6·6%) developed arthritis, 12 (1·7%) developed cutaneous vasculitis, and 6 developed episcleritis. These complications, which were often multiple, occurred six to nine days after the beginning of the illness and three to six days after the start of successful antibiotic therapy. Those patients with severe systemic disease were prone to the complications.
Histological and bacteriological study of the arthritis and vasculitis showed that these lesions were probably not due to persisting infection and suggested that they might be due to immune complex disease.
PMCID: PMC1589774  PMID: 4268766
8.  Comparative study of group A and group C meningococcal infection. 
Archives of Disease in Childhood  1977;52(4):320-323.
114 patients with meningococcal infection were studied; 72 had group C infection and 42 group A infection. 14 patients had acute meningococcaemia, all of whom had group C infection and 9 of whom died. Clinical and laboratory findings were similar in patients with meningitis due to a group A and C organisms, but arthritis and cutaneous vasculitis were more common in patients with group C infection. The overall mortality was 22% in patients with group C infection, and 12% in patients with group A infection, but was the same in both groups when cases of acute meningococcaemia are excluded.
PMCID: PMC1544676  PMID: 860875
9.  Fibrin degradation products in the cerebrospinal fluid of patients with pneumococcal meningitis. 
Raised levels of fibrin degradation products were found in the cerebrospinal fluid of nearly all of 35 patients with pneumococcal meningitis. The mean level was higher in patients who died subsequently than in those who survived. Cerebrospinal fluid from patients with pneumococcal meningitis showed increased fibrinolytic activity as assessed by clot lysis, suggesting local production of fibrin degradation products within the subarachnoid space.
PMCID: PMC1082975  PMID: 501385
10.  Chemotactic activity of cerebrospinal fluid in pyogenic meningitis. 
Journal of Clinical Pathology  1978;31(3):213-216.
Cerebrospinal fluid from patients with pyogenic meningitis was found to be chemotactic for polymorphonuclear neutrophil leucocytes. No significant difference was found between the mean chemotactic activity of cerebrospinal fluid obtained from patients with pneumococcal meningitis or meningococcal meningitis. The chemotactic factor present in cerebrospinal fluid is probably a low molecular weight protein, perhaps a complement component.
PMCID: PMC1145230  PMID: 641194
11.  Amodiaquine Dosage and Tolerability for Intermittent Preventive Treatment To Prevent Malaria in Children ▿ †  
Sulfadoxine-pyrimethamine with amodiaquine (SP-AQ) is a highly efficacious regimen for intermittent preventive treatment to prevent malaria in children (IPTc), but the amodiaquine component is not always well tolerated. We determined the association between amodiaquine dosage by body weight and mild adverse events (AEs) and investigated whether alternative age-based regimens could improve dosing accuracy and tolerability, using data from two trials of IPTc in Senegal, one in which AQ dose was determined by age and the other in which it was determined by weight category. Both dosage strategies resulted in some children receiving AQ doses above the recommended therapeutic range. The odds of vomiting increased with increasing amodiaquine dosage. In one study, incidence of fever also increased with increasing dosage. Anthropometric data from 1,956 children were used to predict the dosing accuracy of existing and optimal alternative regimens. Logistic regression models describing the probability of AEs by dosage were used to predict the potential reductions in mild AEs for each regimen. Simple amendments to current AQ dosing schedules based on the child's age could substantially increase dosing accuracy and thus improve the tolerability of IPTc using SP-amodiaquine in situations where weighing the child is impractical.
PMCID: PMC2825997  PMID: 20065053
12.  Meningococcal infection and proteolytic control. 
Journal of Clinical Pathology  1978;31(12):1177-1181.
Cascade enzyme inhibitors (C1-esterase inhibitor, C3b inactivator, antithrombin III) and other major proteolytic enzyme inhibitors (alpha 1 trypsin inhibitor, alpha 1 chymotrypsin inhibitor, inter-alpha-trypsin inhibitor, alpha 2 macroglobulin) as well as C3 and alpha 1 acid glycoprotein, have been examined in the sera of Nigerian patients suffering from meningococcal infection of varied severity. Patients with meningococcaemia had lower serum concentrations of important inhibitors than did patients with localised meningitic infection. Within the coccaemic group, those who died had the lowest values, notably of antithrombin III and alpha 2 macroglobulin (and also of C3). The clinical end-result of meningococcal infection may be related to the degree of disequilibrium of the linked system of proteolytic control induced by the meningococcal endotoxin.
PMCID: PMC1145527  PMID: 85637
13.  A cerebrospinal fluid leucocidin in pyogenic meningitis. 
Journal of Clinical Pathology  1978;31(7):688-691.
Cerebrospinal fluid (CSF) samples were tested for their cytotoxicity to polymorphonuclear neutrophil leucocytes (PMN) using a 51Cr release assay. Most samples from patients with pyogenic meningitis damaged PMN while normal CSF samples did not. No difference was found between the cytotoxic activity of CSF from patients with pneumococcal meningitis and from patients with meningococcal meningitis. It is, therefore, unlikely that a CSF leucocidin plays an important part in producing the high mortality of pneumococcal meningitis.
PMCID: PMC1145375  PMID: 670425
14.  Cerebrospinal fluid immunoglobulins and complement in meningococcal meningitis. 
Journal of Clinical Pathology  1977;30(8):720-722.
Cerebrospinal fluid (CSF) immunoglobulins (IgA, IgG, IgM) were measured in 107 patients with meningococcal meningitis. Levels were correlated significantly with CSF total protein, and both CSF immunoglobulin and protein increased with age. C3 was measured in the CSF of 38 patients and was also closely correlated with the CSF protein level. C3 breakdown products were found in all six CSFs tested. The CSF immunoglobulin and complement were thought to have leaked from the plasma due to inflammation of the meninges and had little value in diagnosis or prognosis.
PMCID: PMC476532  PMID: 599185
15.  Evidence for familial immune defect in meningococcal meningitis. 
British Medical Journal  1976;1(6020):1247-1250.
Twenty-six patients who had recovered from group A meningococcal meningitis were vaccinated with group C meningococcal polysaccharide and tetanus toxoid. Their haemagglutinating antibody response was measured two weeks later and compared with those of 22 siblings and 39 controls. Patients and siblings had a significantly lower antibody response to the group C vaccine but not to tetanus toxoid. This suggests that patients susceptible to meningococcal disease may have an immune defect involving their response to meningococcal polysaccharides.
PMCID: PMC1639823  PMID: 817771
16.  Complement and meningococcal infection. 
British Medical Journal  1976;1(6013):797-799.
Serum C3 levels were measured in 211 patients with meningococcal disease. Low levels were found in 13 patients with acute meningococcaemia, and complement activation may have contributed to the peripheral circulatory collapse that was responsible for nine deaths. The complement profile of these patients suggested activation of both classical and alternative complement pathways. Patients with meningitis had a higher mean serum C3 level than controls. Serial studies in 13 serum antigen-positive patients with meningitis who subsequently developed arthritis or cutaneous vasculitis showed a transient fall in serum C3 in eight. This fall was probably due to the formation of immune complexes that were responsible for their allergic complications.
PMCID: PMC1639447  PMID: 1260336
17.  Low Incidence of Rheumatoid Factor and Autoantibodies in Nigerian Patients with Rheumatoid Arthritis 
British Medical Journal  1970;1(5688):71-73.
Sera from 53 Nigerian patients satisfying the American Rheumatism Association criteria for a diagnosis of definite or probable rheumatoid arthritis and sera from sick and healthy Nigerian controls were tested for rheumatoid factor, autoantibodies, and immunoglobulin levels. Rheumatoid factor and autoantibodies were found no more frequently in patients with rheumatoid arthritis than in controls. These findings confirm the clinical impression that Nigerian patients with polyarthritis satisfying the criteria for a diagnosis of rheumatoid arthritis differ from Caucasian patients with the disease in a number of important respects. They suggest that either these patients do not have rheumatoid arthritis but a distinct clinical syndrome or that in Nigeria the course of rheumatoid arthritis is modified by genetic or environmental factors.
PMCID: PMC1699135  PMID: 5411447
18.  Immunodiagnosis of Snake Bite 
British Medical Journal  1974;4(5947):743-745.
Management of a patient with snake bite is influenced by the nature of the offending snake. Species diagnosis based on the patient's history and physical signs is often unreliable and the possibility of making a species diagnosis by immunological means has therefore been investigated. Wound aspirates, blister fluids, sera, and urine samples from patients with snake bite were examined for the presence of species-specific venoms using immunodiffusion. A positive species diagnosis was made in 40 out of 101 patients. Immunodiagnosis was especially successful in patients bitten by the puff adder, Bitis arietans, and the African spitting cobra, Naja nigricollis. A higher success rate could probably be achieved using more specific antisera and more sensitive assay techniques.
PMCID: PMC1612756  PMID: 4216390
19.  Bites by the Saw-scaled or Carpet Viper (Echis carinatus): Trial of Two Specific Antivenoms 
British Medical Journal  1974;4(5942):437-440.
Echis carinatus is the most important cause of morbidity and mortality from snake bite in Nigeria and in many other parts of the world. Forty-six patients with systemic poisoning by this snake were given echis antivenom made either by the South African Institute for Medical Research (S.A.I.M.R.) or by Behringwerke (North and West African polyvalent antivenom). A simple test of blood coagulability was used to assess whether an adequate neutralizing dose of antivenom had been given. An average of 15·2 ml S.A.I.M.R. antivenom restored normal coagulability permanently in all 23 patients in one group, but in the other group receiving an average dose of 37·9 ml Behringwerke antivenom normal clotting resulted in only 18 out of 23 patients. Local tissue swelling was similar in both groups, but local necrosis occurred in three patients treated with Behringwerke antivenom and in none given S.A.I.M.R. antivenom.
PMCID: PMC1612524  PMID: 4154124
20.  Allergic Complications of Meningococcal Disease II—Immunological Investigations 
British Medical Journal  1973;2(5869):737-740.
Immunological investigation of four patients with meningococcal meningitis who developed arthritis or cutaneous lesions showed circulating meningococcal antigen at the time of presentation in each patient. It was cleared from the circulation over the next few days. Circulating antibody was detectable in three of the four patients about a week after the onset of the illness. A marked fall in the serum C3 level occurred in two patients at about that time. Deposits of meningococcal antigen, immunoglobulin, and C3 were detected in the synovial fluid white cells of the two patients studied and in one of three skin biopsies examined. These findings suggest that the arthritis and cutaneous lesions of meningococcal meningitis may be due to immune complex formation.
PMCID: PMC1589813  PMID: 4268767
21.  Immunological aspects of nephrotic syndrome in northern Nigeria. 
Archives of Disease in Childhood  1981;56(3):199-202.
Immunological aspects of 40 northern Nigerian children with nephrotic syndrome of recent onset are reported. Eight our of 30 had hepatitis-associated antigen in their sera. Hypocomplementaemia was rare. Measurement of serum C3, C4, and ASOT was not of diagnostic value. Proteinuria selectivity index was poor in half of the patients, and appeared t o depend on the severity of the kidney lesion. Abnormal immunofluorescence of kidney glomeruli to immunoglobulins, complement, Plasmodium malariae, and Plasmodium falciparum was found in 26 of the 29 children. The pattern of immunofluorescence was chiefly granular and was confined to the glomeruli. IgM was predominant. It was concluded that immunological reaction is involved in the pathogenesis of nephrotic syndrome in northern Nigerian children.
PMCID: PMC1627150  PMID: 7011214
22.  Antiglobulins in Nigerians with rheumatoid disease. 
Annals of the Rheumatic Diseases  1975;34(2):142-145.
The levels of IgG and IgM antiglobulins in the sera of Nigerian patients with seropositive rheumatoid arthritis, seronegative arthritis, and Reiter's syndrome have been studied using an immunosorbent of glutaraldehyde insolubilized human IgG. No conclusion could be reached in the case of IgM antiglobulins because of the relatively high threshold of detectability in the quantitation procedure, but all groups of patients had significantly higher levels of IgG antiglobulins than did a group of healthy Nigerians.
PMCID: PMC1006362  PMID: 806269
24.  Lymphocytic infiltration of the brain in sleeping sickness. 
British Medical Journal  1976;2(6047):1291-1292.
Cerebrospinal fluid mononuclear cells from 40 patients with advanced Gambian sleeping sickness were examined for intracytoplasmic immunoglobulin and for B- and T-lymphocyte markers. About 5% of mononuclear cells were plasma cells. Most of the lymphocytes present were B cells. These findings suggest that the considerable lymphocytic infiltration of the nervous system seen in advanced sleeping sickness is not a cell-mediated immune reaction to trypanosomes. Immune complexes may play a part in producing the brain damage characteristic of this disease.
PMCID: PMC1689967  PMID: 1087170
25.  Optimization of a rapid nonisotopic DNA probe assay for Plasmodium falciparum in the Gambia. 
Journal of Clinical Microbiology  1991;29(7):1517-1519.
An enzyme-linked synthetic DNA probe which hybridizes to repetitive DNA of Plasmodium falciparum was used in conjunction with a microtiter-based lysis and filtration blood processing procedure. An assay protocol was developed that is more sensitive and robust than previous protocols, which use stored blood and phenol extraction. In comparison with thick smear examination, 33% positive, 60% negative, and 7% conflicting scores were recorded from 390 analyzed clinical samples, and the sensitivity threshold was about 30 parasites per mm3 of blood.
PMCID: PMC270145  PMID: 1885747

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