Browsing by Author "Mgone, Charles S."

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    Allelic frequencies of p53 codon 72 polymorphism and human papillomavirusmediated cervical cancer In Papua New Guinean women
    (Pacific Journal of Medical Sciences, 2015) Mgone, Charles S.
    Cervical cancer is regarded as a sexually transmitted disease caused by the human papilloma virus (HPV) detected in up to 80 per cent of the cancer biopsies. Genetic susceptibility of a p53 allelic variant has been postulated to play a vital role in carcinogenesis. This study was aimed at determining the allelic frequencies of p53 codon 72 polymorphism in Papua New Guinean women and also assessing the presence of HPV in cervical cancer biopsies. Peripheral blood (3-5 mL) was collected from 53 healthy females of reproductive age (19-37 years) with no known past and current history of HPV infections. Sixty-two cervical biopsies along with cervical swaps were obtained from patients (19-54 years) with clinical symptoms and histopathological confirmation of cervical cancer. DNA was extracted from the peripheral blood samples and cervical samples. Exon 4 was amplified with PCR and further genotypic analyses performed by Restriction fragment length polymorphism (RFLP) and single-stranded conformational polymorphism (SSCP). Of the 53 normal samples analyzed, 3.8 % (2/53) were Arginine homozygous, 58.5 % were Proline homozygous and 37.7 % were heterozygous. For the cancer samples, 14.5 % (9/62) were Arginine homozygous, 54.8 % were Proline homozygous and 30.7% were heterozygous. HPV genome was detected in 83.9 % (52/62) of the cervical cancer samples. The genotypic trend and allelic frequencies were consistent with literature.
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    Amoebic Liver Abscess in Infancy A Case Report
    (University of Zimbabwe, 1983) Mgone, Charles S.
    A case report on infantile amoebic abscess is presented. Pitfalls in the proper diagnosis are mentioned. These include the general belief that the condition is rare and the difficulties encountered in recovery of the offending organisms both in stools and from the liver abscess. The pus itself may also not be characteristic. The need for early diagnosis is emphasized and we recommend draining the abscess and instituting metronidazole.
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    Analysis of Combined Effect of CYP2C19 Genetic Polymorphism and Proton Pump Inhibitors Coadministration on through concentration of Voriconazole
    (Pharmacogenomics and Personalized Medicine, 2021) Mafuru, Magesa; Phillip, Amani; Mgone, Charles S.
    Purpose: To analyze the combined effect of CYP2C19 genetic polymorphism and PPIs coadministration on voriconazole trough concentration (VCZ-Ctrough) in Chinese patients with hematological disorders. Patients and Methods: A prospective observational study involved 250 plasma samples from 114 adult patients receiving voriconazole with or without PPIs were analyzed. Demographics and clinical characteristics were obtained from patient’s records. A validated LC-MS/MS was used to quantify the plasma VCZ-Ctrough. Genotyping for CYP2C19*2 and CYP2C19*3 variant alleles was performed by PCR-RFLP followed by DNA sequencing. The combined total score (from 2 to 5) was calculated for each patient. The higher the score, the lesser the metabolism of the patient. Findings: Fifty percent of patients administered with voriconazole were coadministered with PPIs, predominantly omeprazole or esomeprazole. Patients exhibiting CYP2C19 poor metabolizer phenotype showed a significantly higher median VCZ-Ctrough, (4.31µg/mL [IQR, 1.64µg/mL–7.36µg/mL]) than patients with normal metabolizer (1.38µg/mL, [IQR, 0.79µg/mL–2.14µg/mL], p < 0.0001). Similarly, patients co-administration with PPIs had higher median VCZ-Ctrough (2.86µg/mL [IQR 1.33µg/mL–4.66µg/mL]), than PPIs non-users (1.71µg/mL, [IQR, 0.86µg/mL–3.48µg/mL], p = 0.001). However, we noted that the median VCZ-Ctrough for each factor was ranging within the normal recommended therapeutic range in the Chinese population (0.5µg/mL–5µg/mL). But when the two factors were combined, the median VCZ-Ctrough was steadily increasing as the metabolic capacity (reflected by combined total score) was increasing. Importantly, the median VCZ-Ctrough in PM/PPIs user (total score 5) was significantly elevated to supra-therapeutic levels compared to NM/PPI non-user group (total score 2) (5.83µg/mL [IQR, 2.19µg/mL–9.51µg/mL] versus 1.13µg/mL [IQR, 0.67µg/mL–1.82µg/mL]), respectively, P < 0.0001. Furthermore, we observed that the elevation of median VCZ-Ctrough to supra-therapeutic levels was largely contributed by omeprazole or esomeprazole compared to lansoprazole or pantoprazole. Conclusion: Coadministration with PPIs significantly increased voriconazole trough concentrations and there was an additive effect in CYP2C19 PMs, who were most likely to have supra-therapeutic levels.
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    Analysis of pan-African Centres of excellence in health innovation highlights opportunities and challenges for local innovation and financing in the continent
    (BMC international health and human rights, 2012) Mgone, Charles S.
    A pool of 38 pan-African Centres of Excellence (CoEs) in health innovation has been selected and recognized by the African Network for Drugs and Diagnostics Innovation (ANDI), through a competitive criteria based process. The process identified a number of opportunities and challenges for health R&D and innovation in the continent: i) it provides a direct evidence for the existence of innovation capability that can be leveraged to fill specific gaps in the continent; ii) it revealed a research and financing pattern that is largely fragmented and uncoordinated, and iii) it highlights the most frequent funders of health research in the continent. The CoEs are envisioned as an innovative network of public and private institutions with a critical mass of expertise and resources to support projects and a variety of activities for capacity building and scientific exchange, including hosting fellows, trainees, scientists on sabbaticals and exchange with other African and non-African institutions.
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    Antibodies to Plasmodium falciparum Glycosylphosphatidylinositols: Inverse Association with Tolerance of Parasitemia in Papua New Guinean Children and Adults
    (Infection and immunity, 2002) Mgone, Charles S.
    Individuals living in regions of intense malaria transmission exhibit natural immunity that facilitates persistence of parasitemia at controlled densities for much of the time without symptoms. This aspect of immunity has been referred to as malarial “tolerance” and is thought to partly involve inhibition of the chain of events initiated by a parasite toxin(s) that may otherwise result in cytokine release and symptoms such as fever. Antibodies to the candidate Plasmodium falciparum glycosylphosphatidylinositol (GPI) toxin have been viewed as likely mediators of such tolerance. In this study, the relationship between antibodies to P. falciparum GPIs, age, and parasitemia was determined in asymptomatic children and adults living in Madang, Papua New Guinea. The prevalence and intensity of antibody responses increased with age and were lowest in children 1 to 4 years old with the highest-density parasitemias. In children of this age group who were tolerant of parasitemia during the study, only 8.3% had detectable immunoglobulin G (IgG) and none had IgM antibodies to GPI. This suggests that anti-GPI antibodies are unlikely to be the sole mediator of malarial tolerance, especially in children younger than 5 years. Following antimalarial treatment, clearance of parasitemia led to a fall in anti-GPI IgG response in children and adolescents within 6 weeks. As anti-GPI antibodies potentially play a role in protecting against disease progression, our results caution against the treatment of asymptomatic parasitemia and suggest that generation of a sustained antibody response in children poses a challenge to novel antitoxic vaccination strategies.
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    Application of Direct cDNA Sequencing for the Characterisation of Molecular Pathology in Acute Intermittent Porphyria
    (University of Glasgow, 1991) Mgone, Charles S.
    Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by partial deficiency of the enzyme porphobilinogen deaminase (PBG-D). It is heterogeneous and commonly gene carriers of the disorder remain asymptomatic and may not always be diagnosed by conventional biochemical methods. Since detection of gene carriers is of central importance to the management of this condition, an alternative method of diagnosis is essential. Mutations causing acute intermittent porphyria have not however, been fully characterised. In the current study, direct cDNA sequencing of polymerase chain reaction (PCR) amplified templates has been developed and applied for the characterisation of mutations associated with this disorder. The procedure was developed by amplifying RNA from various sources including human placenta, chorion, lymphocytes and lymphoblastoid cells. The amplification was performed by a technique referred to as reverse-transcriptase polymerase chain reaction (R-T PCR) in which both the first strand cDNA synthesis and the subsequent amplification are performed in the same reaction mixture. Two approaches to the R-T PCR amplification were employed and compared. In the first approach, the first strand cDNA synthesis was carried out with one of the primers complementary to the non-erythroid PBG-D mRNA and in the second, by using oligo(dT)12-18. Both methods were successful and comparable, but the later was preferred because it could be modified in asymmetric PCR to directly produce either the sense or the anti-sense strand. The PBG-D cDNA synthesised and amplified by the R-T PCR was either directly sequenced as double-stranded (ds) templates or eluted and reamplified by asymmetric PCR to produce singlestranded templates. Alternatively, single-stranded templates were produced directly by 'asymmetric' R-T PCR. Prior to sequencing, the PCR amplified templates were concentrated, desalted and purified to remove excess deoxyribonucleoside triphosphates (dNTPs) and amplification primers. Several purification methods were employed and their efficacy compared. These included, spun-column chromatography, nucleic acid chromatography system (NACS) purification, centrifuge-driven dialysis, geneclean TM purification, gel fractionation and selective precipitation in ammonium acetate and propan-2-ol. Selective precipitation with ammonium acetate and propan-2-ol was found to be the simplest and most effective method of template purification. In addition it was also inexpensive, reliable and convenient. Dideoxy sequencing of both double-stranded and single-stranded (ss) templates was performed with either Sequenase T7 DNA polymerase or Taq DNA polymerase. Sequencing of the singlestranded templates, especially when produced by asymmetric reamplification of cDNA gave the most consistent and reliable results. For routine sequencing, there was no difference in the performance of the two sequencing enzymes used, although Taq DNA polymerase was better than Sequenase T7 DNA polymerase in handling templates with complex secondary structures. The procedure of direct sequencing was applied on asymetrically amplified templates of thirty patients with acute intermittent porphyria (AIP) and ten normal controls. The diagnosis of acute intermittent porphyria was based on increased excretion of aminolevulinic acid (ALA) and porphobilinogen (PBG) in urine and decreased activity of erythrocyte porphobilinogen deaminase (PBG-D) coupled with a clinical history of one or more acute attacks. The mean erythrocyte porphobilinogen activity in the acute intermittent porphyria patients was 22. 3 nmol/h/ml erythrocytes. The normal adult activity range for the enzyme is 25-42 nmol/h/ml erythrocytes in the females and 30-48 in males. After optimisation of the R-T PCR, correct sized products were obtained from the amplification of all samples, indicating absence of any major deletions, Sequencing of these products revealed seven point mutations in twelve patients with acute intermittent porphyria and none in the control subjects. All mutations were due to single base substitutions, four of which were associated with amino acid substitutions and are likely to be the cause of AIP in these individuals. The remaining three were silent mutations without change of amino acid and are therefore regarded as neutral polymorphisms. The detected mutations were Q34K (C100→A) seen in two related individuals, L177R (T530→G) also observed in two unrelated individuals, R167Q (G500→A) and H256N (C766→A) each seen separately in single subjects. The silent mutation L42L (G117→A) was seen in one individual whereas S45S (G135→A) and V202V (G606→T) were seen in two and four individuals respectively. With the exception of the mutation R167Q which has been previously reported in four other individuals, the rest of the mutations were novel, emphasising the heterogeneity of this condition. (Abstract shortened by ProQuest.).
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    The association of the glycophorin C exon 3 deletion with ovalocytosis and malaria susceptibility in the Wosera, Papua New Guinea
    (The Journal of the American Society of Hematology, 2001) Mgone, Charles S.
    Erythrocyte polymorphisms, including ovalocytosis, have been associated with protection against malaria. This study in the Wosera, a malaria holoendemic region of Papua New Guinea, examined the genetic basis of ovalocytosis and its influence on susceptibility to malaria infection. Whereas previous studies showed significant associations between Southeast Asian ovalocytosis (caused by a 27– base pair deletion in the anion exchanger 1 protein gene) and protection from cerebral malaria, this mutation was observed in only 1 of 1019 individuals in the Wosera. Polymerase chain reaction strategies were developed to genotype individuals for the glycophorin C exon 3 deletion associated with Melanesian Gerbich negativity (GPCΔex3). This polymorphism was commonly observed in the study population (GPCΔex3 frequency = 0.465, n = 742). Although GPCΔex3 was significantly associated with increased ovalocytosis, it was not associated with differences in either Plasmodium falciparumor P vivax infection measured over the 7-month study period. Future case-control studies will determine if GPCΔex3 reduces susceptibility to malaria morbidity.
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    Bibliometric Assessment of European and Sub-Saharan African Research Output on Poverty-Related and Neglected Infectious Diseases from 2003 to 2011
    (PLoS neglected tropical diseases, 2015) Mgone, Charles S.
    Background The European & Developing Countries Clinical Trials Partnership (EDCTP) is a partnership of European and sub-Saharan African countries that aims to accelerate the development of medical interventions against poverty-related diseases (PRDs). A bibliometric analysis was conducted to 1) measure research output from European and African researchers on PRDs, 2) describe collaboration patterns, and 3) assess the citation impact of clinical research funded by EDCTP. Methodology/ Principal Findings Disease-specific research publications were identified in Thomson Reuters Web of Science using search terms in titles, abstracts and keywords. Publication data, including citation counts, were extracted for 2003–2011. Analyses including output, share of global papers, normalised citation impact (NCI), and geographical distribution are presented. Data are presented as five-year moving averages. European EDCTP member countries accounted for ~33% of global research output in PRDs and sub-Saharan African countries for ~10% (2007–2011). Both regions contributed more to the global research output in malaria (43.4% and 22.2%, respectively). The overall number of PRD papers from sub-Saharan Africa increased markedly (>47%) since 2003, particularly for HIV/AIDS (102%) and tuberculosis (TB) (81%), and principally involving Southern and East Africa. For 2007–2011, European and sub-Saharan African research collaboration on PRDs was highly cited compared with the world average (NCI in brackets): HIV/AIDS 1.62 (NCI: 1.16), TB 2.11 (NCI: 1.06), malaria 1.81 (NCI: 1.22), and neglected infectious diseases 1.34 (NCI: 0.97). The NCI of EDCTP-funded papers for 2003–2011 was exceptionally high for HIV/AIDS (3.24), TB (4.08) and HIV/TB co-infection (5.10) compared with global research benchmarks (1.14, 1.05 and 1.35, respectively). Conclusions The volume and citation impact of papers from sub-Saharan Africa has increased since 2003, as has collaborative research between Europe and sub-Saharan Africa. >90% of publications from EDCTP-funded research were published in high-impact journals and are highly cited. These findings corroborate the benefit of collaborative research on PRDs. Author Summary The European & Developing Countries Clinical Trials Partnership (EDCTP) was created in 2003 as a European response to the global health crisis caused by the three main poverty-related diseases (PRDs) of HIV/AIDS, tuberculosis and malaria. EDCTP funds research focusing on clinical trials for diagnosing, preventing and treating these diseases. We conducted a bibliometric analysis to 1) measure research output and citation impact from European and African researchers working on PRDs, 2) describe collaboration patterns, and 3) assess the citation impact of research funded by EDCTP. Citation analysis is a commonly used bibliometric tool to analyse scientific literature. Overall, the volume and citation impact of papers from sub-Saharan Africa has increased since 2003, as has collaborative research between Europe and sub-Saharan Africa. Papers arising from collaborative research had a higher citation impact than non-collaborative research and >90% of publications from EDCTP-funded research projects were published in high-impact journals. These results suggest that research on PRDs in sub-Saharan Africa is growing and that the EDCTP partnership contributes to high-impact, collaborative research published in high-impact journals. By providing research funds and supporting activities to strengthen the research environment, the partnership contributes to sub-Saharan African researchers taking the lead in PRD research.
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    Birthweight and neonatal outcome at the Muhimbili Medical Centre, Dar Es Salaam, Tanzania
    (East African Medical Journal, 1998) Mgone, Charles S.
    A prospective study of neonatal morbidity and mortality was made over four months in 1990 at the neonatal unit in Muhimbili Medical Centre. The incidence of low birthweight (LBW) was 16%. Seven hundred and eighty four LBW infants and 612 heavier infants admitted for care in the unit were followed up for six weeks. The mean birth weight was 2854 grams. LBW carried a seven-fold increased risk of mortality (291/784;37%); this was 64% (291/341) of the total. The risk of morbidity in LBW infants was increased three-fold (436/784;56%) being 73% (436/598) of the total. Factors significantly associated with increased morbidity and mortality were prematurity, birth asphyxia, sepsis, respiratory distress syndrome, hypothermia and hypoglycaemia. The majority of the deaths (83%) occurred within the first week of life.
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    Cerebral palsy in Dar es Salaam
    (Central African Journal of Medicine, 1990) Mgone, Charles S.
    Between December 1985 and July 1986 a study on cerebral palsy was undertaken among the inpatients and outpatients of the department of Paediatrics and Child Health, Muhimbili Medical Centre Centre, Dar Es Salaam. The objective of the study was to determine the clinical pattern of cerebral palsy and its associated handicaps. During this period, 100 children with cerebral palsy, 56 boys and 44 girls ranging in age between four months and 10 years, were seen. The commonest type of cerebral palsy seen was spastic tetraplegia which occurred in 36 percent of the cases followed by spastic diplegia and hemiplegia seen in 20 and 15 percent of the cases respectively. In 70 children the cerebral palsy was associated with other severe handicaps, the commonest being epilepsy which occurred in 35 percent of the children followed by deafness, speech disorders and blindness. Birth asphyxia, convulsions of undetermined causes, low birth weight, meningitis and cerebral birth trauma were found to be the leading causes of cerebral palsy. As these conditions are largely preventable or amenable to treatment, it is suggested that improvement of antenatal and perinatal care is important in the reduction of the incidence of cerebral palsy.
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    Chlamydia Trachomatis Infection and Distribution of Serovars in the Eastern Highlands Province, Papua New Guinea
    (Papua New Guinea Medical Journal, 2007) Mgone, Charles S.
    We have used nested polymerase chain reaction (PCR) and the PCR-based endonuclease digestion method to genotype Chlamydia trachomatis serovars in 460 infected individuals from the Eastern Highlands Province of Papua New Guinea. Our study groups comprised women who presented in labour to the Goroka Base Hospital, their newborn infants, symptomatic children who presented to the hospital's Outpatients Department and men and women from 15 randomly selected villages in the Asaro Valley. In this analysis, the major outer membrane protein (MOMP) gene, omp1, of C. trachomatis was amplified using DNA obtained from the endocervix of women, urine from men, and both the eye and nasopharynx of children. Amplified DNAs were digested concurrently using Alul and a combination of EcoRI, Hinl and Hpall restriction enzymes. The mixtures were separated on electrophoretic gels and the respective serovars designated on the basis of resolved digested DNA patterns. Our results, which were confirmed also by omp1 sequence data, show serovars D, E, F, G, H and L3 to be present in the studied communities. The overall relative frequencies of these serovars were 30%, 21%, 25%, 1%, 20% and 2% respectively, with serovars D, E, F and H accounting for 97% of these infections. Double infections among these principal serovars were also detected in all our study groups but at a low overall frequency of 3%. Serovar D was the major agent involved in the aetiology of chlamydial infection in both children and adults though serovar F was the most frequent in newborn infants. Serovar H was relatively less frequent in symptomatic children. No trachoma-related serovars were detected, confirming the rarity of this disease in Papua New Guinea. In contrast, although clinical cases of lymphogranuloma venereum have not been described in the country, the detection of serovar L3 in this study suggests that it may occur. However, the association of L3 also with childhood infection indicates that it may be causing the same pathology as the serovars D-K that are associated with non-ulcerative sexually transmitted infections.
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    Clinical presentation of subacute sclerosing panencephalitis in Papua New Guinea
    (Tropical Medicine & International Health, 2003) Mgone, Charles S.
    Eighty‐three children presented at Goroka Base Hospital in the Eastern Highlands Province (EHP) of Papua New Guinea over a period of 3 years and 9 months between February 1997 and November 2000 were confirmed to have subacute sclerosing panencephalitis (SSPE). Confirmation of the diagnosis was based on the demonstration of high titres of measles antibodies in the cerebrospinal fluid and/or serum in association with clinical features supportive of SSPE, including characteristic electroencephalographic changes and amplification of measles virus genome by reverse transcriptase polymerase chain reaction in some cases. The mean cerebrospinal fluid and serum enzyme immunoassay antibody levels among the SSPE patients were 38 250 and 860 580, respectively. The mean age of onset of SSPE was 7.9 ± 2.6 years and ranged between 2 and 14 years. The overall male to female ratio was 1.2:1 and 1.4:1 for EHP.
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    Collaborative approaches to clinical trials
    (Global Forum for Health Research, 2008) Mgone, Charles S.
    Scientific research of ten tends to be driven by opportunit y rather than purpose. Many scientists consciously or subconsciously conduct research on issues that are presumed to be topical merely because they are either popular, controversial or are attractive to funders. The results of such research studies tend to be duplicative, repetitive and even outright wasteful. Such outcomes can be avoided by conducting tailor- made research programmes designed to answer specific questions prioritized according to public health needs. Several public–private partnerships (PPPs) and product development partnerships (PDPs) have been founded to promote the conduct of focused research and development to solve specific health problems. 1.Many of these partnerships have concentrated on diseases of povert y.2 However, such custom- built and purposedriven research programmes are also not free of peril since the centralization and control of research may lead to the suppression of competitiveness and creativit y. This approach is quite of ten tied to a top- bot tom strategy, where the funder defines the research agenda, sets the priorities and conducts the research activities.This approach of ten bypasses or minimally involves partners at the bot tom, which in this case happens to be researchers and policy.makers in developing countries, where the diseases being investigated are endemic. Such an approach should be avoided at all costs. A situation where ‘he who pays the piper calls the tune’ must never arise. All stakeholders,especially those from developing countries, must be fully involved in the planning of clinical trials. 2 The European and Developing Countries Clinical Trials Partnership (EDCTP) was founded to accelerate research and the development of new or improved inter vention tools against diseases of povert y, specifically HIV, malaria and tuberculosis (TB), through the conduct of clinical trials. To achieve and sustain this, the partnership must be genuine with equal commitment and full participation, including planning and implementation by both sets of partners. However, to achieve true partnership, the capacit y of developing country partners to conduct clinical trials according to international standards, and using best practices, must be built and strengthened. changing as we become increasingly aware that to ensure the success and sustainabilit y of many North–South collaborative programmes, developing country partners must be empowered to fully participate and co- own these programmes. One of the ways EDCTP is encouraging this is by integrating capacit y development and networking components into clinical trial grants. The capacit y development component is used to ensure the successful completion of the clinical trials and ser ves as a practical exercise through ‘learning by doing’ thus enabling the developed capacit y to be utilized immediately, enhancing skill retention and sustainabilit y.The networking component allows for technology transfer and, through South–South mentorship, proliferation of capacit y among the participating developing country partners.
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    Community based study of sexually transmitted diseases in rural women in the highlands of Papua New Guinea: prevalence and risk factors
    (Sexually transmitted infections, 1998) Mgone, Charles S.
    Objective: To estimate the prevalence of sexually transmitted diseases (STDs) and determine their risk factors/markers among a rural population of women in the highlands of Papua New Guinea. Methods: Community based random cluster sample of women of reproductive age were interviewed and examined and had specimens collected for laboratory confirmation of chlamydial and trichomonal infection, gonorrhoea, syphilis, and bacterial vaginosis. Results: Chlamydia trachomatis was detected in 26%, Trichomonas vaginalis in 46%, Neisseria gonorrhoeae in 1%, syphilis in 4%, pelvic inflammatory disease (PID) (diagnosed clinically) in 14%, and bacterial vaginosis in 9% of 201 women. 59% of the women had at least one STD. In a multivariate logistic regression analysis taking the clustered sampling into account, independent risk factors for chlamydial infection were age < 25 years, < four living children, visualisation of yellow mucopurulent endocervical secretions on a white swab, and bacterial vaginosis. Being married to a man who did not have other wives was protective. For trichomonal infection, independent risk factors were having no formal education, infertility, more than one sexual partner in the previous 12 months, treatment for genital complaints in the previous 3 months, abnormal vaginal discharge detected on examination, and chlamydial infection. Similar levels of trichomonal infection were found in all age groups. Among married women, rates of infection correlated with their perception of their husband having had other sexual partners in the previous 3 months, and this relationship was significant for chlamydial infection among women over 25. Conclusion: STDs are a major problem in this population, with the risk factors varying by outcome. Current treatment regimens are inappropriate given the high prevalence of trichomonal infection, and the available services are inadequate. Effective interventions are required urgently to reduce this burden and to prevent the rapid transmission of HIV.
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    Conquering malaria: enhancing the impact of effective interventions towards elimination in the diverse and changing epidemiology
    (Journal of global infectious diseases, 2011) Mgone, Charles S.
    Malaria remains a major global disease burden causing just under a million deaths each year, mainly of children and pregnant women in sub-Saharan Africa. It consumes up to 40% of public health expenditure of these poor countries, causing in Africa US$ 12 billion in lost GDP every year. This should not be acceptable since malaria is preventable, and there is clear evidence that optimal use of current tools can reduce much of the suffering and deaths. Three major factors allowing this to happen include: (i) inadequate funding to implement a massive initial surge, to achieve universal coverage, (ii) weak country capacities for rapid scale up of such interventions and little or no use of evidence-guided methods, and (iii) insufficient coordination of efforts between national programmes, donors and technical agencies in strategic planning for sustaining gains and in building capacity. We discuss the importance of the surge and the kind of approaches that would accelerate the pace toward elimination and eventual eradication.
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    A continuing high incidence of subacute sclerosing panencephalitis (SSPE) in the Eastern Highlands of Papua New Guinea
    (Epidemiology & Infection, 2003) Mgone, Charles S.
    The aims of this descriptive study were to confirm the high incidence of subacute sclerosing panencephalitis (SSPE) previously reported from Papua New Guinea (PNG) and to relate SSPE to previous measles vaccination and measles illness. From February 1997 to April 1999 we diagnosed a total of 55 patients with SSPE at Goroka Base General Hospital in Eastern Highlands Province (EHP) of PNG. The diagnosis was based on high cerebrospinal fluid and serum measles virus antibody titres with progressive neurological disorder and myoclonic jerks. Of these 55 patients 42 were from EHP, including 32 whose onset was in the 2-year period 1997–1998. The annual incidence of SSPE in EHP in these 2 years was 98 per million population under 20 years of age, the highest ever reported. This incidence was more than ten times higher than the highest incidence in the prevaccine era reported from elsewhere. The mean age of onset of SSPE was 7·7 years (range 2·8–14·8 years) and the interval between measles and the onset of SSPE, where known, had a mean of 5·9 years and a range of 2·5–11·1 years. Among the SSPE patients 19 had a documented history of measles vaccination. Eight of these 19 also had documentation of previous measles illness; of these, seven were vaccinated after the development of measles and one was vaccinated 20 days before measles illness. Two non-SSPE children received vaccination twice which was documented and subsequently developed measles which was also substantiated by documentation. Two patients with SSPE yielded amplified nucleotide sequences of measles virus that were different from any of the vaccine strains. We found no evidence to implicate measles vaccination in the development of SSPE.
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    Control measures and the outcome of the measles epidemic of 1999 in the Eastern Highlands Province.
    (Papua New Guinea Medical Journal, 1999) Mgone, Charles S.
    In the Eastern Highlands Province (EHP) of Papua New Guinea (PNG) measles outbreakshave occurred regularly every 3 to 4 years since 1980. The latest was between September 1998and March 2000. Between July 1999 and March 2000 314 children with measles were reviewedat Goroka Base Hospital. The majority of these children were very young: 55% were under 1year and 27% under 6 months. The median age of the measles cases was 11 months (range 10days to 13 years). 40% of the children had a verifiable history of having received at least onedose of measles vaccine. The majority were vaccinated during the epidemic and includedmany children who either were below 6 months of age or who developed measles within 2weeks of vaccination. Measles complications occurred in 82% of the children, the mostcommon being pneumonia. Serious complications, particularly severe pneumonia, were morecommon among the unvaccinated children than in those who had received at least a single doseof the measles vaccine. No deaths occurred among 82 children who had received measlesvaccine more than 2 weeks before the onset of clinical measles, compared with 10 deaths in 206children who had never been vaccinated against measles or were vaccinated in the 2 weeksbefore presentation (p=0.067). The overall case fatality was 4%: 14% among the hospital-acquired and 2.5% in community-acquired measles. Improvement in the measles vaccinationcoverage and supplementary vaccination campaigns are required to prevent measles outbreaksin PNG. Intensified measles vaccination campaigns, such as the one conducted in EHP in 1999,are recommended during epidemics to minimize deaths due to measles and to rapidly controloutbreaks. The efficacy of measles vaccination can only be measured in total mortality, not inthe prevention of clinical meales
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    The correlation between microscopical examination and erythrocyte band 3 (AE1) gene deletion in South-east Asian ovalocytosis
    (Transactions of the Royal Society of Tropical Medicine and Hygiene, 1998) Mgone, Charles S.
    South-east Asian ovalocytosis status was determined by microscopical examination of peripheral blood samples collected from 137 individuals in Papua New Guinea. The examination was performed separately by 2 microscopists, one of whom was very experienced in examining peripheral blood films for the diagnosis of south-east Asian ovalycytosis and the other was recently trained. The samples were also analysed by polymerase chain reaction (PCR) to determine ovalocytosis status by demonstrating a 27 base pair deletion in erythrocyte band 3 protein of the affected individuals. The microscopists were unaware of each other's results and of those obtained by PCR. Generally, there was very good agreement between the results obtained by both microscopists and the PCR. Although there was considerable inter-observer variation in the final ovalocyte count between the 2 microscopists, this did not affect their ability to discriminate between ovalocytic and normocytic individuals. Taking the PCR results as the standard, for the first, more experienced observer, the most efficient ovalocyte count cut-off point was around 50%. At this ovalocyte count the sensitivity and specificity of microscopical examination were 93·6% and 92·2%, and the positive and negative predictive values 86·3% and 96·5%, respectively. The second microscopist generally underscored the ovalocyte counts and his most efficient cut-off point was 20%, with sensitivity and specificity of 85·1% and 93·3% and positive and negative predictive values of 87·0% and 92·3%, respectively.
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    Correspondence:strengthening capacity, collaboration and quality of clinical research in Africa: EDCTP Networks of Excellence
    (Tanzania journal of health research, 2009) Mgone, Charles S.
    Developing countries bear 90% of the global disease burden, but only access about 10% of globally available health research funding. Weak south–south networking hampers effective use of limited resources, production of critical mass of quality scientists, career opportunities and incentives to retain the few available scientists. The south must urgently act strategically to accelerate generation of talented scientists, create enabling environment and incentives to retain scientists and attract back those in diaspora. The creation of strong networks of excellence for clinical research among southern academic and research institutions is a novel strategic approach championed by European and Developing Countries Clinical Trials Partnership to achieve the aforementioned goals and mitigate the high disease burden. It will promote strong collaboration, resource sharing and cross-mentorship allowing each partner to grow with complementary capacities that support each other rather than compete negatively. It will enable the south and Africa in particular to participate actively and own the means for solving its own health problems and raise the professional quality and capacity of southern institutions to forge better and equal partnership with northern institutions.