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Amodiaquine alone, amodiaquine+sulfadoxine-pyrimethamine, amodiaquine+artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial
(2005) Mutabingwa, Theonest K.
Background Many countries in Africa are considering a change to combination treatment for falciparum malaria because of the increase in drug resistance. However, there are few effectiveness data for these combinations. Our aim was to study the effectiveness of three drug combinations that have proven efficacious in east Africa compared with amodiaquine monotherapy. Methods We undertook a randomised trial of antimalarial drug combinations for children (aged 4–59 months) with uncomplicated malaria in Muheza, Tanzania, an area with a high prevalence of resistance to sulfadoxine-pyrimethamine and chloroquine. Children were randomly allocated 3 days of amodiaquine (n=270), amodiaquine +sulfadoxine-pyrimethamine (n=507), or amodiaquine+artesunate (n=515), or a 3-day six-dose regimen of artemether-lumefantrine (n=519). Drugs were taken orally, at home, unobserved by medical staff. The primary endpoint was parasitological failure by day 14 assessed blind to treatment allocation. Secondary endpoints included day 28 follow-up and gametocyte carriage. Analysis was by intention to treat. Findings Of 3158 children screened, 1811 were randomly assigned treatment and 1717 (95%) reached the 14-day follow-up. The amodiaquine group was stopped early by the data and safety monitoring board. By day 14, the parasitological failure rates were 103 of 248 (42%) for amodiaquine, 97 of 476 (20%) for amodiaquine+sulfadoxine-pyrimethamine, 54 of 491 (11%) for amodiaquine+artesunate, and seven of 502 (1%) for artemether-lumefantrine. By day 28, the parasitological failure rates were 182 of 239 (76%), 282 of 476 (61%), 193 of 472 (40%), and 103 of 485 (21%), respectively. The difference between individual treatment groups and the next best treatment combination was significant (p<0·001) in every case. Recrudescence rates by day 28, after correction by genotyping, were 48·4%, 34·5%, 11·2%, and 2·8%, respectively. Interpretation The study shows how few the options are for treating malaria where there is already a high level of resistance to sulfadoxine-pyrimethamine and amodiaquine. The WHO-packaged six-dose regimen of artemether-lumefantrine is effective taken unsupervised, although cost is a major limitation.
Amodiaquine and Artemether-Lumefantrine Select Distinct Alleles of the Plasmodium falciparum mdr1 Gene in Tanzanian Children G. S. Humphreys, Treated for Uncomplicated Malaria
(Antimicrobial agents and chemotherapy, 2007) Mutabingwa, Theonest K.
The artemisinin-based combination therapies artemether-lumefantrine (AL) and amodiaquine (AQ) plus artesunate have been adopted for treatment of Plasmodium falciparum malaria in many African countries. Molecular markers of parasite resistance suitable for surveillance have not been established for any of the component drugs in either of these combinations. We assessed P. falciparum mdr1 (Pfmdr1) alleles present in 300 Tanzanian children presenting with uncomplicated falciparum malaria, who were enrolled in a clinical trial of antimalarial therapy. Pfmdr1 genotype analysis was also performed with isolates from 182 children who failed AQ monotherapy and 54 children who failed AL treatment. Pfmdr1 alleles 86Y, 184Y, and 1246Y were more common among treatment failures in the AQ group than among pretreatment infections. The converse was found in the AL-treated group. Children presenting with the 86Y/184Y/1246Y Pfmdr1 haplotype and treated with AQ were significantly more likely to retain this haplotype if they were parasite positive during posttreatment follow-up than were children treated with AL (odds ratio, 33.25; 95% confidence interval, 4.17 to 1441; P, <0.001). We conclude that AL and AQ exert opposite within-host selective effects on the Pfmdr1 gene of P. falciparum.
Ancillary-care responsibilities in observational research: two cases, two issues
(The Lancet, 2007) Mutabingwa, Theonest K.
International collaborative research in developing countries raises difficult ethical issues in the setting of severe diseases and complex costly treatments. Discussion of two matters has characterized the debate on this type of research. First, what standard of care should be provided to participants in intervention studies, particularly those in control groups? 1,2,3,4 Second, what level of benefits should be provided to individuals and communities during a study and after completion, particularly with respect to treatments proven effective through research? 4, 5, 6 Here, we focus on a third issue, investigators' responsibilities for meeting participants' needs for ancillary care.
Antimalarial drugs in pregnancy: a review
(Bentham Science Publishers, 2006) Mutabingwa, Theonest K.
In this review we examine the available information on the safety of antimalarials in pregnancy, from both animal and human studies. The antimalarials that can be used in pregnancy include (1) chloroquine, (2) amodiaquine, (3) quinine, (4) azithromycin, (5) sulfadoxine-pyrimethamine, (6) mefloquine, (7) dapsone-chlorproguanil, (8) artemisinin derivatives, (9) atovaquone-proguanil and (10) lumefantrine. Antimalarial drugs that should not be used in pregnancy including (1) halofantrine, (2) tetracycline/doxycycline, and (3) primaquine. There are few studies in humans on the pharmacokinetics, safety and efficacy of antimalarials in pregnancy. This is because pregnant women are systematically excluded from clinical trials. The absence of adequate safety data, especially in the first trimester, is an important obstacle to developing treatment strategies. The pharmacokinetics of most antimalarial drugs are also modified in pregnancy and dosages will need to be adapted. Other factors, including HIV status, drug interactions with antiretrovirals, the influence of haematinics and host genetic polymorphisms may influence safety and efficacy. For these reasons there is an urgent need to assess the safety and efficacy of antimalarial treatments in pregnancy, including artemisinin based combination therapies.
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.
Artemisinin combination therapies
(The Lancet, 2006) Mutabingwa, Theonest K.
Global mortality from Plasmodium falciparum malaria has always been enormous, and has increased in recent decades as chloroquine-resistant parasites spread worldwide. Alarms were raised further when parasites developed resistance to sulfadoxine-pyrimethamine soon after it was introduced to replace chloroquine in many areas. To protect the few remaining drugs in the malaria armamentarium, combination therapy is now touted, particularly combinations that include artemisinin derivatives, widely known as artemisinin combination therapies (ACTs).
Artemisinin-based combination therapies (ACTs): Best hope for malaria treatment but inaccessible to the needy!
(Acta tropica, 2005) Mutabingwa, Theonest K.
Artemisinin-based combination therapies (ACTs) are the best anti-malarial drugs available now. Artemisinin enhances efficacy and has the potential of lowering the rate at which resistance emerges and spreads. Under low transmission intensity, ACTs have an additional public health benefit of reducing the overall malaria transmission and studies are urgently needed to investigate modalities of attaining similar benefits under high transmission. Despite being recommended by WHO since 2001, overall deployment of ACT has been slow. Limiting factors are high cost, limited knowledge and public awareness on the concept of combination therapy (CT) and ACT in particular, limited knowledge on safety of ACTs in pregnancy, operational issue such as inappropriate drug use, lack of suitable drug formulations, lack of post-marketing surveillance (PMS) systems, and the imbalance between demand and supply. Through concerted efforts of multilateral organizations, the local scientific community with involvement of policy-makers progress has been on several fonts leading to improved ACT uptake rates in the last 2 years. Of 43 countries that had adopted ACT by February 2005, 18 (42%) adopted the policy in 2004. Preference to co-formulated Coartem has led to a surge in its demand with consequent shortage. Alternative ways for increased production of ACTs are urgently needed otherwise most policies will remain adopted on paper. Despite limitations, opportunities are opening up for effective malaria control. Insecticides, insecticide-treated nets (ITNs) and ACTs are proven efficacious controls available that should be accessed by many. Substantial funding is now available for biomedical malaria research and for policy implementation. While the Global Fund is the financial engine behind the scaling up of ACT uptake, delays in cash flow after grant approval has led to many countries adopting ACT in 2004 but only few (nine) implementing it. Clear policies on granted funds and minimal politics within funding agencies might improve the situation. Increased interest in drug development together with the public and private sector partnership have led to new anti-malarials, some less expensive and therefore affordable by poor malaria endemic countries. Dihydroartemisinin-piperaquine (Artekin) has a cost advantage over other ACTs (US$ 1 for an adult treatment) making it a potential best candidate for deployment in Africa. Part of available funds should be invested into capacity building and strengthening (personnel, resources and infrastructure) of institutions in malaria endemic countries. This will create enabling environment and a critical mass of scientists and public health experts to spearhead ACT policy implementation. Active involvement of scientists from malaria endemic countries in recent International Scientific Forums like the Malaria in Pregnancy Working Group and the Consortium on ACT Implementation is the best way forward to emulate.
Assessing healthcare providers’ knowledge and practices relating to insecticide-treated nets and the prevention of malaria in Ghana, Laos, Senegal and Tanzania
(Malaria journal, 2014) Ndossi, Godwin D.
Background: Research evidence is not always being disseminated to healthcare providers who need it to inform their clinical practice. This can result in the provision of ineffective services and an inefficient use of resources, the implications of which might be felt particularly acutely in low- and middle-income countries. Malaria prevention is a particularly compelling domain to study evidence/practice gaps given the proven efficacy, cost-effectiveness and disappointing utilization of insecticide-treated nets (ITNs). Methods: This study compares what is known about ITNs to the related knowledge and practices of healthcare providers in four low- and middle-income countries. A new questionnaire was developed, pilot tested, translated and administered to 497 healthcare providers in Ghana (140), Laos (136), Senegal (100) and Tanzania (121). Ten questions tested participants’ knowledge and clinical practice related to malaria prevention. Additional questions addressed their individual characteristics, working context and research-related activities. Ordinal logistic regressions with knowledge and practices as the dependent variable were conducted in addition to descriptive statistics. Results: The survey achieved a 75% response rate (372/497) across Ghana (107/140), Laos (136/136), Senegal (51/ 100) and Tanzania (78/121). Few participating healthcare providers correctly answered all five knowledge questions about ITNs (13%) or self-reported performing all five clinical practices according to established evidence (2%). Statistically significant factors associated with higher knowledge within each country included: 1) training in acquiring systematic reviews through the Cochrane Library (OR 2.48, 95% CI 1.30-4.73); and 2) ability to read and write English well or very well (OR 1.69, 95% CI 1.05-2.70). Statistically significant factors associated with better clinical practices within each country include: 1) reading scientific journals from their own country (OR 1.67, 95% CI 1.10-2.54); 2) working with researchers to improve their clinical practice or quality of working life (OR 1.44, 95% CI 1.04-1.98); 3) training on malaria prevention since their last degree (OR 1.68, 95% CI 1.17-2.39); and 4) easy access to the internet (OR 1.52, 95% CI 1.08-2.14). Conclusions: Improving healthcare providers’ knowledge and practices is an untapped opportunity for expanding ITN utilization and preventing malaria. This study points to several strategies that may help bridge the gap between what is known from research evidence and the knowledge and practices of healthcare providers. Training on acquiring systematic reviews and facilitating internet access may be particularly helpful.
Assessment of cancer registries (CR) in low- and middle-income countries (LMCs)
(Assessment of cancer registries (CR) in low-and middle-income countries (LMCs), 2012) Ntabaye, Moshi K.
Background: CRs are crucial for cancer control, yet few global standards exist. This study identifies characteristics of quality CRs in LMCs and globally. Methods: A Medline search was conducted in PubMed to identify peer-reviewed articles describing: 1) CR development and functionality 2) types of CRs and 3) implementation, development and utility of CRs in LMCs. We examined articles describing CRs and assessed benchmarking data that could be used to define quality characteristics. Full-text, English-language articles were reviewed. References cited were searched for additional articles. We categorized characteristics into 4 domains: comparability, completeness, validity and timeliness. Results: The literature search yielded 16 key characteristics within 4 domains that may define high quality CRs. In the “comparability” domain, the key characteristic was use of standard definitions. CRs in the US, Europe and China generally adhere to the International Classification of Diseases for Oncology and histological verification of disease; in 2007 only 40% of African registries did so. In the “completeness” domain the key characteristic was population coverage. African CRs monitor 8% of the population, the Costa Rican registry covers 90%, US and Madras cancer registries reach 96%. In the “validity” domain the key criterion was pathologic diagnosis confirmation. Most LMC CRs are not pathology-based. CRs in wealthier settings like Hong Kong report histologic confirmation in >85% of cases. In the “timeliness” domain standards for timely data reporting are largely undocumented. Conclusions: No consensus exists on characteristics of quality CRs in a global context. The current study provides an initial set of metrics. A Delphi panel of international experts is planned to further address this. Based on this literature review, CRs in LMCs have limited reporting, validation and regional population coverage.
Assessment of parental perception of malaria vaccine in Tanzania
(Malaria journal, 2015) Semali, Innocent A.
Background Clinical trials of the RTS,S malaria vaccine have completed Phase III and the vaccine is on track for registration. Before making decisions about implementation, it is essential to prepare the ground for introducing the vaccine by assessing awareness and willingness to use malaria vaccines and to provide policy makers with evidence-based information on the best strategies to engage communities to manage the introduction of malaria vaccine in Tanzania. Methods In November 2011, as part of a large cross-sectional study of all 23 regions of Tanzania (mainland Tanzania and Zanzibar) was conducted during Tanzanian Integrated Measles Campaign (IMC) survey. In this study, the variables of interests were awareness and willingness to use a malaria vaccine. The main outcome measure was willingness to use a malaria vaccine. Logistic regression was used to examine the influence of predictive factors. Results A representative sample of 5502 (out of 6210) women, aged 18 years or older and with children under 11 months old, was selected to participate, using random sampling probability. Awareness of the forthcoming malaria vaccine, 11.8 % of participants in mainland Tanzania responded affirmatively, compared to 3.4 % in Zanzibar (p value <0.0001). 94.5 % of all respondents were willing to vaccinate their children against malaria, with a slight difference between mainland Tanzania (94.3 %) and Zanzibar (96.8 %) (p value = 0.0167). Conclusions Although mothers had low awareness and high willingness to use malaria vaccine, still availability of malaria vaccine RTS,S will compliment other existing malaria interventions and it will be implemented through the Immunization, Vaccines and Biologicals (IVB) programme (formerly EPI). The information generated from this study can aid policy makers in planning and setting priorities for introducing and implementing the malaria vaccine.
Associations and healers: Attitudes towards collaboration in Tanzania. In The professionalisation of African medicine
(Routledge, 2018) Semali, Innocent A.
The establishment of an effective organisation or association of healers may be considered as one step towards the professionalisation of traditional healers. In Tanzania there is no law which prohibits or governs the practice of traditional medicine. In Tanzania there have been a number of efforts to promote traditional medicine. The association (UWATA) attracted many traditional healers within the urban set-up, some of whom were not traditional healers but quacks, while others were opportunists. Many people have urged the incorporation or collaboration of traditional medicine with modern health care. In general, traditional healers have been eager to form associations but faced with leadership problems. Umoja wa Waganga Tanzania or Traditional Healers' Union of Tanzania managed to open a number of treatment centres in the country. Its members were always coming forward to display their talents to cure, and they organised several treatment sessions in a number of areas throughout the country.
Asymtomatic parasitaemia and placental malaria infection among pregnant women in Kigoma urban District, Western Tanzania.
(East African Journal of Public Health, 2006) Kabalimu, Titus K.
Objective: To determine the magnitude of malaria infection and anaemia among pregnant women in Kigoma Municipality, western Tanzania. Setting: An urban maternal and child health clinic (MCH) located in the Kigoma Municipality in western Tanzania. Methods: A cross-sectional study was conducted in an urban MCH clinic in Kigoma Municipality. Informed consent to participate in the study was sought from each pregnant woman. Consenting Pregnant women were interviewed to solicit for socio-demographic characteristics and information relating to use of malaria preventive measures. The women were also examined for anaemia and malaria parasitaemia. At delivery, the women were also examined for malaria infection of the placenta. The research was cleared by the Ethical Clearance Committee of the Muhimbili University College of Health Sciences, Dar es Salaam. Data were managed and analysed using SPSS/PC+ for windows. Results: The mean age of the pregnant women was 26.7 years (SD = 5.4) with the youngest woman being 14 years and the oldest being 45 years. The response proportion to participate in the study was 96.7% (N= 705). It was found that 8.4% of the women examined had asymptomatic malaria parasitaemia while2.8% had malaria infection of the placenta. Women with placental malaria were more likely to deliver low birth weight babies than others (8.8% versus 2.1%. Pregnant women who reported using bednets were less likely to have placental malaria compared to those not using bednet (2.2% versus 3.3%). Similarly, pregnant women who reported using bednets were less likely to have asymptomatic malaria parasitaemia than others (5.9% versus 10.4%). Conclusions: We conclude that placental malaria occurs in Kigoma municipality and it appears that use of bednets might be an effective strategy in controlling malaria among pregnant women in Tanzania.
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.
Bridging the gaps among research, policy and practice in ten low- and middle-income countries: Development and testing of a questionnaire for researchers
(Health Research Policy and Systems, 2010) Ndossi, Godwin D.
Background: A questionnaire could assist researchers, policymakers, and healthcare providers to describe and monitor changes in efforts to bridge the gaps among research, policy and practice. No questionnaire focused on researchers’ engagement in bridging activities related to high-priority topics (or the potential correlates of their engagement) has been developed and tested in a range of low- and middle-income countries (LMICs). Methods: Country teams from ten LMICs (China, Ghana, India, Iran, Kazakhstan, Laos, Mexico, Pakistan, Senegal, and Tanzania) participated in the development and testing of a questionnaire. To assess reliability we calculated the internal consistency of items within each of the ten conceptual domains related to bridging activities (specifically Cronbach’s alpha). To assess face and content validity we convened several teleconferences and a workshop. To assess construct validity we calculated the correlation between scales and counts (i.e., criterion measures) for the three countries that employed both and we calculated the correlation between different but theoretically related (i. e., convergent) measures for all countries. Results: Internal consistency (Cronbach’s alpha) for sets of related items was very high, ranging from 0.89 (0.86- 0.91) to 0.96 (0.95-0.97), suggesting some item redundancy. Both face and content validity were determined to be high. Assessments of construct validity using criterion-related measures showed statistically significant associations for related measures (with gammas ranging from 0.36 to 0.73). Assessments using convergent measures also showed significant associations (with gammas ranging from 0.30 to 0.50). Conclusions: While no direct comparison can be made to a comparable questionnaire, our findings do suggest a number of strengths of the questionnaire but also the need to reduce item redundancy and to test its capacity to monitor changes over time.
Capacity and capability of Tanzania health facilities to diagnose and manage diabetes mellitus in pregnancy
(Diabetes research and clinical practice, 2018) Mutabingwa, Theonest K.
ABSTRACT Aims Gestational Diabetes Mellitus (GDM) remains a neglected cause of maternal and foetal morbidity and mortality in developing countries exacerbated by limited screening and management strategies. This study aimed to understanding how the RCH health system works in Tanzania, so as to provide opportunity for improving GDM screening and management. Methods A questionnaire was administered to facility staff and physical performance observed in 30 randomly selected public RCH facilities. Results Deficiencies identified included limited understaffing, late booking at ANC, and limited screening for GDM due to lack of equipment and supplies. Most women (96%) attending ANCs and postnatal care (87%) were managed at respective facilities with only 12% and 22% respectively being referred to higher levels of care. Facility staff were less trained or received fewer refresher courses in diabetes (0–5%), hypertension (4–6%), and other NCDs (0–16%) compared to training in PMCTC (39%), management of postpartum bleeding (31%) and HIV/AIDs (31%). Conclusion Diabetes during pregnancy is rarely sought in public health facilities and its management is suboptimal. Training and refresher courses of staff in diabetes and hypertension should be uplifted and health systems should be strengthened to improve capacity and capability of facilities for better quality of care.
Case management of malaria in pregnancy
(The Lancet infectious diseases, 2007) Mutabingwa, Theonest K.
In all malarious areas, infection by any of the main human plasmodial species during pregnancy is detrimental to the mother and the fetus. These potentially fatal infections must be prevented, but when they develop they require prompt diagnosis and treatment. Current tools to detect malaria parasites in pregnant women are often not used and remain too insensitive to detect a low parasitaemia. The kinetics, safety, and efficacy of available antimalarial drugs are poorly documented because pregnant women are systematically excluded from clinical trials. A considerable effort, involving clinical trials, is urgently required to improve the diagnosis and case management of malaria during pregnancy if the morbidity and mortality of maternal malaria is to be reduced.
Cervical cancer prevention in Tanzania: Health services and health policy influences on a preventable cancer
(Research gate, 2010) Semali, Innocent A.
Background: Cervical cancer is the leading cause of cancer death among women in Tanzania. Fewer than 20% of women in Tanzania present for care when cervical cancer disease is in its early, preventable stages. Development of structural factors related to health policy and health services may alleviate disease mortality and morbidity. Methods: Fifty stakeholders from government, nongovernmental, and healthcare organizations including the Tanzanian Ministry of Health (MOH) completed semi-structured face-to-face interviews to determine existing health services for cervical cancer, and capacity for implementation of a community-based program to promote screenings. Each interview lasted approximately two hours and was comprised of individuals and teams of stakeholders. Qualitative data analyses were performed using NVivo software. Results: Qualitative themes were related to political will, health services infrastructure, and partnership building. Political will and public/private collaboration exists for the development of a program to facilitate screenings for cervical cancer. The MOH committed to improve health services by increasing capacity for cervical cancer screen and treat protocols. Additionally, a public/private team will develop a strategic plan for cervical cancer control and prevention to define specific health policies and screening recommendations. Conclusion: Increasing the capacity for cervical cancer screenings will improve reproductive health services for women. Additionally, the development of cervical cancer screening policies may decrease deaths and presentation of late stage disease. Cervical cancer prevention is a public health imperative for women in low resource settings. It is a preventable cancer and therefore a major social justice issue affecting women, their families and communities.
Chloroguanide metabolism in relation to the efficacy in malaria prophylaxis and the S‐mephenytoin oxidation in Tanzanians
(Clinical Pharmacology & Therapeutics, 1996) Mutabingwa, Theonest K.
S‐Mephenytoin and chloroguanide (proguanil) oxidation was studied in 216 Tanzanians. The mephenytoin S/R ratio in urine ranged from <0.1 to 1.16. The distribution was skewed to the right, without evidence of a bimodal distribution. Ten subjects (4.6%, 2.2% to 8.3%, 95% CI) with an S/R mephenytoin ratio >0.9, were arbitrarily defined as poor metabolizers of mephenytoin. The chloroguanide/cycloguanil ratio ranged from 0.82 to 249. There was a significant correlation between the mephenytoin S/R ratio and the chloroguanide/cycloguanil ratios (rs = 0.73; p < 0.00001). This indicates that cytochrome P4502C19 or CYP2C19 is a major enzyme that catalyzes the bioactivation of chloroguanide to cycloguanil. Chloroguanide is a pro‐drug, and hence a low CYP2C19 activity may lead to prophylactic failure caused by inadequate formation of cycloguanil. Fifty‐eight women who previously took either 200 mg chloroguanide daily (n = 26) or 200 mg chloroguanide daily plus 300 mg chloroquine weekly (n = 32) in a malaria chemoprophylaxis study showed that there was a significant correlation between the number of earlier breakthrough parasitemia episodes and the chloroguanide/cycloguanil ratio (rs = 0.30; p = 0.02). The breakthrough rate did not correlate with the S/R mephenytoin ratio. However, other factors, such as exposure to mosquitoes and sensitivity of the plasmodium to cycloguanil, are probably more important.
Chloroquine therapy still useful in the management of malaria during pregnancy in Muheza, Tanzania
(Tropical and geographical medicine, 1991) Mutabingwa, Theonest K.
In searching for effective malaria chemosuppressives during pregnancy in Muheza District--Tanzania, pregnant women are randomly given either 300 mg base chloroquine once weekly or 200 mg daily proguanil. Breakthroughs presenting with clinical malaria are treated with 25 mg base chloroquine/kg (25 CQ) over three days. Due to loss of malaria immunity during pregnancy and Muheza moderate levels and degrees of chloroquine resistance, the in vivo response to 25 CQ was monitored. Between March and May 1989, 49 women were treated resulting into 32 (65%) parasitological clearances and 17 (35%) failures within 7 days. Two of 17 failures (12%) exhibited RIII response and the remaining 15 (88%) had a favourable clinical response. Only 6 (19%) of 32 cleared patients either recrudesced or got reinfected during the three weeks follow up period. In addition to its safety and affordability, the observed drug efficacy during peak malaria transmission and inspite of prevailing resistance makes 25 CQ an ideal first line drug for the management of malaria during pregnancy.
Chloroquine-resistant plasmodium falciparum at the Tanganyika planting company(TPC) sugar estate,moshi,Tanzania.
(World Health Organization, 1985) Mutabingwa, Theonest K.
From 1966 to 1978 the TPC maintained a mass malaria chemoprophylactic programme based on chloroquine.However after reports of treatment failure to 25 mg chloroquine base per kg body weight,the sensitivity of plasmodium falciparum to chloroquine at the TPC sugar estate near Moshi,northern Tanzania,was determined.In Vivo and In vitro test utilizing standard methods were carried out on semi-immune asymptomatic primary-school children whose ages ranged from 8 to 18 years,with a mean age of 12 years.These children were selected from a total of 746 school children who had been screen for malaria parasites and of whom 245(32.8%)were found to be to be positive.

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