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Antimalarial treatment with artemisinin combination therapy in Africa desirable, achievable, but not easy
(BMJ, 2005) Mutabingwa, Theonest K.
The steady increase of drug resistant malaria across Africa is a crisis for which there are achievable solutions, but no easy ones. The scale of the problem is not in doubt. In Africa malaria remains one of the commonest causes of death and serious morbidity, especially for children and pregnant women.1 Despite a decision in principle by many countries in Africa to use artemisinin based combination therapies (ACTs), most cases of malaria are still treated with monotherapy and in many areas most of these treatments will fail.2 3 Drug combinations, rather than monotherapy, are now seen to be the best solution for treating malaria, and artemisinin based drug combinations are highly effective, with cure rates similar to that of chloroquine 30 years ago. They seem to be a good long term choice for most African countries, being safe and well tolerated (with the caveat that their safety in early pregnancy is not yet clear). Compared with other antimalarials, ACTs can reduce gametocyte carriage and thereby lower the risk of infectiousness in those who take treatment. In areas of relatively low malaria transmission in South East Asia and South Africa, widespread use of ACTs has reduced significantly the burden of malaria.4 This benefit is likely be less marked in areas of very high transmission in Africa, where much of the reservoir of malaria infection is in asymptomatic people who never seek treatment.
Averting a malaria disaster in Africa where does the buck stop?
(Bulletin of the World Health Organization, 2004) Mutabingwa, Theonest K.
The serious threat posed by the spread of drug-resistant malaria in Africa has been widely acknowledged. Chloroquine resistance is now almost universal, and resistance to the successor drug, sulfadoxine-pyrimethamine (SP), is growing rapidly. Combination therapy has been suggested as being an available and potentially lasting solution to this impending crisis. However, the current cost of combination therapy, and especially that of artemisinin combination therapy (ACT), is potentially a serious drawback, even if a significant part of its cost is passed on to the end-user. If the question of cost is not successfully addressed this could lead to adverse results from the deployment of combination therapy as first-line treatment. These adverse effects range from an increase in potentially fatal delays in infected individuals presenting to medical services, to exclusion of the poorest malaria sufferers from receiving treatment altogether. Urgent steps are needed to reduce the cost of combination therapy to the end-user in a sustainable way if it is to be usable, and some possible approaches are discussed.
Decreased susceptibility to Plasmodium falciparum infection in pregnant women with iron deficiency
(The Journal of infectious diseases, 2008) Mutabingwa, Theonest K.
Abstract Iron plus folate supplementation increases mortality and morbidity among children in areas of malaria endemicity in Africa, but the effects of supplementation on pregnant women in malaria-endemic areas remain unclear. In northeastern Tanzania, where malaria and iron deficiency are common, we found that placental malaria was less prevalent (8.5% vs. 47.3% of women; P < .0001) and less severe (median parasite density, 4.2% vs. 6.3% of placental red blood cells; P = .04) among women with iron deficiency than among women with sufficient iron stores, especially during the first pregnancy. Multivariate analysis revealed that iron deficiency (P < .0001) and multigravidity (P = .002) significantly decreased the risk of placental malaria. Interventional trials of iron and folate supplementation during pregnancy in malaria-endemic regions in Africa are urgently needed to ascertain the benefits and risks of this intervention.
Peripheral adenosine deaminase 1 activity is a biomarker for placental malaria and inflammation.
(American Journal of Obstetrics & Gynecology, 2006) Mutabingwa, Theonest K.
Objective Placental malaria (PM) complicated by placental inflammation is associated with low birthweight (LBW) at delivery, and has been estimated to cause 75,000 to 200,000 infant deaths per year in sub-Saharan Africa. Peripheral blood smears detect parasitemia in only about half of women with PM, making diagnosis difficult. Our objective is to find a simple, inexpensive prenatal test that can detect PM and inflammation and thereby identify pregnant women who are at the highest risk for delivery of LBW infants. Study design Placental and peripheral blood samples were obtained from consenting women age 18-45 years who delivered in Muheza, Tanzania, an area of intense malaria transmission. Microscopy of placental blood and placental tissue sections was used to detect PM and inflammation in mothers delivering singleton infants. Quantitative reverse transcriptase PCR and immunostaining were performed for adenosine deaminase 1 (ADA1). Total ADA plasma activity was assessed using a colorimetric assay, and ADA isotyping was performed by the addition of an ADA1 inhibitor, EHNA. Results Placental ADA1 mRNA levels were elevated during infection and correlated with inflammation. By immunohistochemistry, ADA1 protein was demonstrated to be produced only in PM-positive placentas, in maternal polynuclear cells located in intervillous spaces. Plasma ADA activity was elevated in women with PM compared to those without (p<0.001), in women with PM and inflammation compared to those with PM only (p=0.002), and in mothers of LBW infants compared to mothers of normal birthweight infants (p=0.01). Isotyping indicated that ADA1 is the predominant plasma isotype of women with PM. We estimate that the cost of reagents to measure ADA1 is approximately $0.01 per test. Conclusion Plasma ADA1 activity is a simple and inexpensive test that may help to identify those women with PM who are at risk of LBW infants. Applied prenatally, this assay could allow more intensive anti-malarial treatment of women with inflammatory PM and thereby potentially improve outcomes for their infants.
Prevalence and aetiology of juvenile skeletal ﬂuorosis in the south-west of the Hai district, Tanzania – a community-based prevalence and case–control study
(Tropical Medicine and International Health, 2013) Ndossi, Godwin D.
Introduction Fluorosis is endemic throughout the East African Rift valley, including parts of Tanzania. The aim of the study was to identify all cases of deforming juvenile skeletal fluorosis (JSF) in a northern Tanzanian village and to document the extent of dental fluorosis (DF). Methods Door‐to‐door prevalence survey of all residents of the village. Residents were assessed for the presence of DF and JSF. Those with JSF and randomly selected controls from the same age range were further assessed for possible JSF risk factors. Results The village had a population of 1435. DF was endemic within the population, being present in 911 (75.5%; 95% CI, 73.0–77.9) of dentate individuals who were examined (n = 1207). JSF was present in 56 of 1263 people examined, giving a prevalence of 4.4% (95% CI, 3.3–5.6) and was more common in males. Low body mass index, drinking predominantly well water 3 years previously, not being weaned on bananas, the use of fluoride salts in cooking during childhood and drinking more cups of tea per day were independent predictors of JSF. Conclusions Juvenile skeletal fluorosis is a common and preventable public health problem. Providing clean, low‐fluoride, piped water to affected communities is of obvious health benefit.
Research ethics committees in Africa: authors’ reply
(PLoS Med, 2007) Ndossi, Godwin D.
We thank Dr. Benatar [1] for pointing out that South Africa has two Fogarty-funded bioethics training programs: one that focuses primarily on providing short-term training to mid-career professionals from Southern Africa; and another that provides modular training in research ethics to professionals from the African continent. In addition, there are now several other Fogarty-funded trainingprograms that either target African professionals exclusively or include African professionals, among others, in their programs (see http:⁄⁄www.fi c.nih.gov/programs/training grants/bioethics/index.htm). All of these programs share the goal of increasing professional capacity in bioethics and research ethics on the African continent. Our own paper demonstrated that training even a small number of individuals can make a difference in changing policy and practice regarding research ethics in several institutions; that so many training efforts are now ongoing is a major step forward. Again, having more people teaching and discussing researchethics and starting and staffing research ethics committees will never itself guarantee that research with humans is more ethical, but it seems to be a critical first step. Capacity development for Africa still remains a challenge and worthy of increasing investments in global health
The Structure and Function of Research Ethics Committees in Africa:
(PLoS medicine, 2007) Ndossi, Godwin D.
According to international guidelines [1,2] and several nations’ laws [3–5], research with humans requires independent ethics committee review. In the United States, committees are called institutional review boards (IRBs) [6]; elsewhere they generally are called research ethics committees (RECs). Committees are designed to: provide third party review, thereby minimizing confl icts of interest; protect the welfare of research participants through attention to risks, benefi ts, and informed consent; and avoid exploitation of vulnerable individuals and populations. Most literature examining RECs comes from wealthier countries. One US study found “serious concerns” with the quality of 14% of IRB reviews [7]. Another found that IRBs focused predominantly on consent documentation, spending less time examining voluntariness, selection of participants, and risk [8]. Many US [9–15] and international [16–18] studies have found that different research ethics committees reach different conclusions when reviewing the same study. Several scholars and advisory bodies have made recommendations to address challenges facing US IRBs [19–22]. However, there has been little research examining procedures, strengths, and challenges of RECs in developing countries. Two case reports describe disagreements between host and sponsoring country RECs [23,24], and an international survey reports differences in sponsoring and host country reviews [25]. Three articles describe RECs within one country (Turkey [26], Granada [27], and Sudan [28]), and fi ve within a larger region. MethodsThe Johns Hopkins Bloomberg School of Public Health received a training grant from the Fogarty International Center in 2000 to train three African professionals in bioethics each year [33]. Several of these professionals explicitly seek to increase the scholarly and administrative capacity of their African RECs. In 2004, program faculty and trainees created a structured questionnaire to document the history, composition, functioning, fi nancing, strengths, and challenges of RECs with which the trainees were affi liated. Questionnaires were completed by e-mail. Follow up e-mails clarifi ed responses. Data were entered into Microsoft Excel and tabulated. Trainees and faculty met for two days in 2005 to refi ne concepts and work on the manuscrip Results of Our Case Study Eleven of the 12 trainees who attended the program in 2001–2004 collaborated. Nine had personal experience on one or more African REC. Another trainee secured information from her institution’s REC; one contributed no data. One trainee worked with two committees in his country; another worked with two committees from two countries. Twice, two trainees from the same country were affi liated with different RECs. Thus, twelve RECs were included in this case study from nine African countries: Democratic Republic of the Congo, Ghana (2), Kenya, Nigeria, South Africa (2), Sudan (2), Tanzania, Zambia, and Zimbabwe.Two RECsRivera described 20 RECs in Latin America, fi nding that only 45% had standard operating procedures and that members had limited training [29]. Coker examined RECs in Central and Eastern Europe [30]. Ten countries had national committees, most committees included non-medical members, and three provided training. The World Health Organization’s (WHO) Southeast Asian Regional Offi ce, fi nding that only some of the 16 respondents had national RECs, called for capacity development in the area of research ethics [31]. The WHO African Regional Offi ce found that 36% of member countries had no REC. In the countries that did have RECs, most RECs met monthly, fi ve met quarterly, and one never met [32]. Finally, Milford examined African RECs’ resource needs in the context of HIV vaccine trial preparedness, fi nding that 97% believed African RECs had inadequate training in ethics and HIV vaccine trials and 80% believed African RECs had inadequate training in health research ethics. Additional information on how African RECs function, including their staffi ng, operating procedures, strengths, and challenges would be useful for African and international researchers working within Africa, and for growing efforts to enhance ethics capacity on this vast continent. We therefore used a case study approach to shed light on the structure and functioning of RECs in Africa.

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