Strengthening capacity, collaboration and quality of clinical research in Africa: EDCTP Networks of Excellence.

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.

Biological and haematological safety profile of oral amodiaquine and chloroquine in healthy volunteers with or without Plasmodium falciparum infection in northeast Tanzania.

Amodiaquine (AQ), an effective antimalarial drug for uncomplicated malaria, has been greatly restricted after cases of life-threatening agranulocytosis and hepatic toxicity during prophylactic use. We conducted a hospital based open-label randomised clinical trial in 40 indigenous semi-immune healthy adult male volunteers with and without malaria parasites. The objective was to collect data on biological and haematological safety, tolerability, and parasitological efficacy to serve as baseline in the evaluation of the effectiveness of AQ preventive intermittent treatment against malaria morbidity in infants. Volunteers were stratified according to parasitaemia status and randomly assigned 20 participants each arm to three days treatment with either AQ or chloroquine (CQ). The level of difference of selected haematological and hepatological values pre-and post-trial were marginal and within the normal limits. Clinical adverse effects mostly mild and transient were noticed in 33.3% CQ treated-aparasitaemic, 23.8% of CQ treated-parasitaemic, 28.6% ofAQ-treated parasitaemic and 14.3% of aparasitaemic receiving AQ. Amodiaquine attained 100% parasitological clearance rate versus 70% in CQ-treated volunteers. The findings indicate that there was no agranulocytosis or hepatic toxicity suggesting that AQ may pose no public health risk in its wide therapeutic dosage uses. Larger studies are needed to exclude rare adverse effects.

Capacity of healthcare facilities in the implementation of direct observed treatment strategy for tuberculosis in Arumeru and Karatu districts, Tanzania.

Directly Observed Treatment Short course strategy (DOTS) has proved to have potential improvement in tuberculosis (TB) control in Tanzania. The objective of this cross sectional study was to assess the capacity of health facilities in implementing DOTS, in Arumeru and Karatu districts, Tanzania. Information sought included the capacity to offer TB service and availability of qualified staff and equipment for TB diagnosis. Information on availability and utilization of TB registers and treatment outcome for the year 2004 were also collected. A total of 111 health facilities were surveyed, 86 (77.5%) in Arumeru and 25 (22.5%) in Karatu. Only 23.4% (26/111) facilities were offering TB treatment services in the two districts. Majority 17/26 (65.38%) of them were government owned. Thirty eight (44.7%) facilities were offering TB laboratory services. All facilities with TB services (TB laboratory investigation and treatment) had TB registers. Seventy two (85.0%) of health facilities which do not provide any TB services had qualified clinical officers and at least a microscopy. Of the 339 cases notified in Arumeru in 2004, 187 (60.7%) had treatment outcome available, 124 (66.3%) were cured and 55 (29.4%) completed treatment. In Karatu 638 cases were notified in 2004, 305 (47.8%) had treatment outcome available, 68 (22.3%) cured and 165 (54.1%) completed treatment. In conclusion, the overall capacity for implementing DOTS among the facilities surveyed is found only in about 20% and 30% for clinical and laboratory components of DOTS, respectively. The capacity to provide TB diagnosis and treatment in Karatu district was relatively lower than Arumeru. It is important that capacity of the facilities is strengthened concurrently with the planned introduction of community-based DOTS in Tanzania.

Smokeless tobacco use among adolescents in Ilala Municipality, Tanzania.

Smokeless tobacco use is a significant part of the overall world tobacco problem. When the habit is introduced early in life, it increases the chance for permanent addiction and primes adolescents for use of harder drugs, exposing them to higher risk of oral cancer and other adverse effects of tobacco. This baseline study aimed at providing descriptive information on smokeless tobacco knowledge and use among adolescents at a time just before the ban on such products was enforced nationally on 1st December 2006. Six out of 101 primary and four out of 11 secondary schools were randomly selected in Ilala Municipality, Tanzania. A total of 1011 students were randomly selected and interviewed; boys (mean age = 14.5 years) accounted for 50.7% and girls (mean age = 13.6 years) 49.3%. The prevalence of tobacco use was 5.9% (boys = 9%; girls = 2.4%). Prevalence of smokeless tobacco use was 3.6%, about half of all who have ever smoked. Most popular brand of smokeless tobacco reported was Kuberi (44.8%) followed by Gutka (6.9%). Twelve (41%) of the smokeless tobacco users were using the products almost everyday. Among the reasons reported for smokeless tobacco use were pleasure (27.6%), smell (17.2%) and taste (6.9%). However, 48.3% of the users did not know why they used the product for the first time. Smokeless tobacco products were branded as nutritional supplements with different tastes and strengths, ideal for enticing the curiosity of adolescents. Given the crafty practice of the tobacco industry and salesmen, there is need for monitoring of availability of these products in circulation and enforcement of the ban nationally and globally to institute measures for effective elimination of this harmful practice.

Smokeless Tobacco Use among Adolescents in Ilala Municipality; Tanzania

Smokeless tobacco use is a significant part of the overall world tobacco problem. When the habit is introduced early in life; it increases the chance for permanent addiction and primes adolescents for use of harder drugs; exposing them to higher risk of oral cancer and other adverse effects of tobacco. This baseline study aimed at providing descriptive information on smokeless tobacco knowledge and use among adolescents at a time just before the ban on such products was enforced nationally on 1st December 2006. Six out of 101 primary and four out of 11 secondary schools were randomly selected in Ilala Municipality; Tanzania. A total of 1011 students were randomly selected and interviewed; boys (mean age= 14.5 years) accounted for 50.7and girls (mean age= 13.6 years) 49.3. The prevalence of tobacco use was 5.9(boys= 9; girls= 2.4). Prevalence of smokeless tobacco use was 3.6; about half of all who have ever smoked. Most popular brand of smokeless tobacco reported was Kuberi (44.8) followed by Gutka (6.9). Twelve (41) of the smokeless tobacco users were using the products almost everyday. Among the reasons reported for smokeless tobacco use were pleasure (27.6); smell (17.2) and taste (6.9). However; 48.3of the users did not know why they used the product for the first time. Smokeless tobacco products were branded as nutritional supplements with different tastes and strengths; ideal for enticing the curiosity of adolescents. Given the crafty practice of the tobacco industry and salesmen; there is need for monitoring of availability of these products in circulation and enforcement of the ban nationally and globally to institute measures for effective elimination of this harmful practice

Capacity of Healthcare Facilities in the Implementation of Direct Observed Treatment Strategy for Tuberculosis in Arumeru and Karatu Districts; Tanzania

Directly Observed Treatment Short course strategy (DOTS) has proved to have potential improvement in tuberculosis (TB) control in Tanzania. The objective of this cross sectional study was to assess the capacity of health facilities in implementing DOTS; in Arumeru and Karatu districts; Tanzania. Information sought included the capacity to offer TB service and availability of quali?ed staff and equipment for TB diagnosis. Information on availability and utilization of TB registers and treatment outcome for the year 2004 were also collected. A total of 111 health facilities were surveyed; 86 (77.5) in Arumeru and 25 (22.5) in Karatu. Only 23.4(26/111) facilities were offering TB treatment services in the two districts. Majority 17/26 (65.38) of them were government owned. Thirty eight (44.7) facilities were offering TB laboratory services. All facilities with TB services (TB laboratory investigation and treatment) had TB registers. Seventy two (85.0) of health facilities which do not provide any TB services had qualifed clinical offcers and at least a microscopy. Of the 339 cases notified in Arumeru in 2004; 187 (60.7) had treatment outcome available; 124 (66.3) were cured and 55 (29.4) completed treatment. In Karatu 638 cases were noti?ed in 2004; 305 (47.8) had treatment outcome available; 68 (22.3) cured and 165 (54.1) completed treatment. In conclusion; the overall capacity for implementing DOTS among the facilities surveyed is found only in about 20and 30for clinical and laboratory components of DOTS; respectively. The capacity to provide TB diagnosis and treatment in Karatu district was relatively lower than Arumeru. It is important that capacity of the facilities is strengthened concurrently with the planned introduction of community-based DOTS in Tanzania

Biological and Haematological Safety Profile of Oral Amodiaquine and Chloroquine in Healthy Volunteers with or without Plasmodium falciparum Infection in Northeast Tanzania

Amodiaquine (AQ); an effective antimalarial drug for uncomplicated malaria; has been greatly restricted after cases of life-threatening agranulocytosis and hepatic toxicity during prophylactic use. We conducted a hospital based open-label randomised clinical trial in 40 indigenous semi-immune healthy adult male volunteers with and without malaria parasites. The objective was to collect data on biological and haematological safety; tolerability; and parasitological efficacy to serve as baseline in the evaluation of the effectiveness of AQ preventive intermittent treatment against malaria morbidity in infants. Volunteers were stratified according to parasitaemia status and randomly assigned 20 participants each arm to three days treatment with either AQ or chloroquine (CQ). The level of difference of selected haematological and hepatological values pre-and post-trial were marginal and within the normal limits. Clinical adverse effects mostly mild and transient were noticed in 33.3CQ treated-aparasitaemic; 23.8of CQ treated-parasitaemic; 28.6of AQ-treated parasitaemic and 14.3of aparasitaemic receiving AQ. Amodiaquine attained 100parasitological clearance rate versus 70in CQ-treated volunteers. The findings indicate that there was no agranulocytosis or hepatic toxicity suggesting that AQ may pose no public health risk in its wide therapeutic dosage uses. Larger studies are needed to exclude rare adverse effects

Health research agenda for East Africa in the new millennium: looking ahead.

The Regional East African Health Research agenda was presented as a keynote speech during the first East African Health and Scientific Conference, held in Kampala, Uganda from 28th to 30th March 2007. The agenda was developed through a critical analysis of the global, African and Regional East African health challenges and mitigating strategies, taking into account the Millennium Development Goals (MDG), the Abuja declaration and the New Partnership for African Development as background environment, within which the agenda will operate. It is proposed to establish a joint mechanism for research coordination, promotion and regulation; establish stronger collaborative mechanisms for research and training; create a joint Regional East African Community health research and development fund; create joint intellectual property rights protection mechanism; enhance patenting and link research to industry; create a mechanism to enhance translation of research to policy and practice; strengthen clinical research capacities; and strengthen innovation and discovery research capacities. Effective implementation of this agenda will greatly raise the profile and quality of research in the region and improve the health status of the East African populations.

The quality of sputum smear microscopy diagnosis of pulmonary tuberculosis in Dar es Salaam, Tanzania.

This study was carried out to determine the rate of agreement or disagreement of microscopy reading and culture positivity rate among smear positixe and negative specimens between peripheral tuberculosis diagnostic centres (PDCs) and Central Reference luberculosis laboratory (CTRL). In this study 13 PDCs in Dar es Salaam, Tanzania were involved. Lot Quality Assurance Sampling (LQAS) method was used to collect 222 sputum smear slides. A total of 190 morning sputum specimens with corresponding slides were selected for culture. First readings were done by technicians at PDCs and thereafter selected slides and specimens were sent to CTRL for re-examination and culture. Culture results were used as a gold standard. Of 222 slides selected, 214 were suitable for re-examination. Percentage of agreement of smear reading between PDCs and CTRL was 42.9% and 100% for positive and negative slides, respectively. Measure of agreement (Kappa statistic) was 0.5, indicating moderate agreement. Of 190 samples cultured, percentage of agreement between smear reading from PDCs and CTRL was 37% and 88.9% for smear positive and negative slides, respectively. Kappa statistic was 0.3 indicating poor-fair agreements. Comparison of smear reading from PDCs with culture showed sensitivity of 36.9% and specificity of 88.9%. Comparison of smear readings from CTRL with culture results showed sensitivity of 95.6% and specificity of 98.6%. In conclusion there was inadequate performance in diagnosis of TB using smear microscopy among peripheral diagnostic centres in Dar es Salaam. This calls for immediate and rigorous measures to improve the quality of smear microscopy. It is therefore important to strengthen the capacity of laboratory personnel in smear microscopy techniques through supportive supervision and training.

Quality of HIV laboratory testing in Tanzania: a situation analysis.

Tanzania is scaling up prevention, treatment, care and support of individuals affected with HIV. There is therefore a need for high quality and reliable HIV infection testing and AIDS staging. The objective of this study was to assess laboratories capacities of services in terms of HIV testing and quality control. A baseline survey was conducted from December 2004 to February 2005 in 12 laboratories which were conveniently selected to represent all the zones of Tanzania. The questionnaires comprised of questions on laboratory particulars, internal and external quality control for HIV testing and quality control of reagents. Source and level of customer satisfaction of HIV test kits supply was established. Of 12 laboratories, nine used rapid tests for screening and two used rapid tests for diagnosis. In the 12 laboratories, four used double ELISA and five used single ELISA and three did not use ELISA. Confirmatory tests observed were Western Blot in three laboratories, DNA PCR in two laboratories, CD4 counting in seven laboratories, and viral load in two laboratories. Although all laboratories conducted quality control (QC) of the HIV kits, only two laboratories had Standard Operating Procedures (SOPs). Internal and external quality control (EQC) was done at varied proportions with the highest frequency of 55.6% (5/9) for internal quality control (IQC) for rapid tests and EQC for ELISA, and the lowest frequency of 14.3% (1/ 7) for IQC for CD4 counting. None of the nine laboratories which conducted QC for reagents used for rapid tests and none of the five which performed IQC and EQC had SOPs. HIV kits were mainly procured by the Medical Store Department and most of laboratories were not satisfied with the delay in procurement procedures. Most of the laboratories used rapid tests only, while some used both rapid tests and ELISA method for HIV testing. In conclusion, the survey revealed inadequacy in Good Laboratory Practice and poor laboratory quality control process for HIV testing reagents, internal and external quality control.

Quality of HIV laboratory testing in Tanzania: a situation analysis

Tanzania is scaling up prevention; treatment; care and support of individuals affected with HIV. There is therefore a need for high quality and reliable HIV infection testing and AIDS staging. The objective of this study was to assess laboratories capacities of services in terms of HIV testing and quality control. A baseline survey was conducted from December 2004 to February 2005 in 12 laboratories which were conveniently selected to represent all the zones of Tanzania. The questionnaires comprised of questions on laboratory particulars; internal and external quality control for HIV testing and quality control of reagents. Source and level of customer satisfaction of HIV test kits supply was established. Of 12 laboratories; nine used rapid tests for screening and two used rapid tests for diagnosis. In the 12 laboratories; four used double ELISA and five used single ELISA and three did not use ELISA. Confirmatory tests observed were Western Blot in three laboratories; DNA PCR in two laboratories; CD4 counting in seven laboratories; and viral load in two laboratories. Although all laboratories conducted quality control (QC) of the HIV kits; only two laboratories had Standard Operating Procedures (SOPs). Internal and external quality control (EQC) was done at varied proportions with the highest frequency of 55.6(5/9) for tnternal quality control (IQC) for rapid tests and EQC for ELISA; and the lowest frequency of 14.3(1/ 7) for IQC for CD4 counting. None of the nine laboratories which conducted QC for reagents used for rapid tests and none of the five which performed IQC and EQC had SOPs. HIV kits were mainly procured by the Medical Store Department and most of laboratories were not satisfied with the delay in procurement procedures. Most of the laboratories used rapid tests only; while some used both rapid tests and ELISA method for HIV testing. In conclusion; the survey revealed inadequacy in Good Laboratory Practice and poor laboratory quality control process for HIV testing reagents; internal and external quality control

Implication of diethylcarbamazine induced morbidity and the role of cellular responses associated with bancroftian filariasis pathologies.

Pre and post-diethylcarbamazine treatment clinical expression, microfilaraemia prevalence and cellular responses were investigated in individuals in Tanga, Tanzania. Fifty-seven male individuals (aged = 15 years old) were identified for further studies on IL-4, IL-6, IL-8. IFN-gamma, IL-beta, TNF-alpha and nitric oxide in plasma and hydrocoele fluid. Microfilarial prevalence in the examined individuals was 12% with a geometric mean intensity (GMI) of 838 mff/ml in a community with a population of 1018 individuals. Microfilaraemic hydrocoele stage II and III were the most frequent pathologies observed with prevalence of 17.5% and 42. 1 %, respectively. All study individuals treated with diethylcarbamazine (DEC) standard dose of 6 mg/kg experienced post-treatment adverse events. There was no direct relationship between elevated IL-6 and the occurrence and severity of clinical adverse effects post-treatment. The findings from this study suggests that, blood elevated cytokine profile is not the main etiological factor in the inflammatory responses developing after treatment of bancroftian filariasis infections and pathology with DEC. Plasma levels of cellular (cytokines) responses during treatment revealed a proportion of symptomatic patients. Prior to treatment, patients with hydroecoele had high levels of IL-6 than those without the pathology. In conclusion these findings do not support the hypothesis that pro-inflammatory cytokines are directly responsible for adverse events to DEC chemotherapy in bancroftian filariasis infections and pathologies such as hydrocoele, lymphoedema and elephantiasis.

The relationship between malaria parasitaemia and availability of healthcare facility in Mpwapwa district, central Tanzania.

A study was carried out in six villages located at different altitudes in Mpwapwa district of central Tanzania to determine malaria parasitaemia and transmission levels in villages with or without health care facilities. A total of 1119 schoolchildren (age = 5.9-12.3 years) were examined for malaria parasitaemia. Plasmodiumfalciparum was the predominant malaria species accounting for 92.8% of all species. The average malaria prevalence rate among schoolchildren was 25.8% (range 1.5-53.8%). The geometric mean parasite densities for P.falciparum was 361 (N = 286). Higher malaria prevalence was observed in villages at lower (< 1000 m) than at intermediate (1000-1500m) or higher (> 1500m) altitudes. Schoolchildren in areas with health care facilities were less at risk of acquiring malaria by 33.4% as compared with those living in areas without health facilities. Mean packed cell volume in schoolchildren was 38.5% (range = 35.2-41.0%). Splenomegaly was observed in 18.1% (0-40.2%) of the schoolchildren examined and it was higher among those in villages without health care facilities. Anopheles gambiae sensu lato was the only malaria vector found in the district and was found in all villages and at all altitudes. Sporozoite rate in An. gambiae s.l. ranged from 0-10.5%, with the lowland villages recording the highest rates. This study indicates that altitude and geographical accessibility to healthcare service are important determinants of malaria infection among rural communities in Tanzania.

Hospital-based safety and tolerability study to assess efficacy of oral doxycycline in the treatment of Wuchereria bancrofti infection in north-eastern Tanzania.

A hospital based open-label clinical trial of 19 apparently healthy adult males with microfilaraemia was conducted to assess safety, tolerability and efficacy of doxycycline on Wuchereria bancrofti. Study individuals were assigned 8 weeks treatment with doxycycline 200 mg daily. The results of different selected tests showed that, the haematological, hepatic, renal and clinical parameters pre-and post-drug administrations were within the normal range for all treated individuals. Clinical adverse events were mild, transient, tolerable and reported in 7/19 (36.8%) of the study cohort. The mf clearance rate was 100% at 12 months post treatment for the 13 individuals who completed the follow up. These findings indicate that, although the drug was administered for a long period, there was no evidence of toxicity to the myocardium, hepatocytes, renal, bone marrow and blood cells, suggesting that an 8-week course of 200 mg/day doxycycline is a safe and tolerable regime for the treatment of Wuchereria bancrofti infections.

Malaria epidemics in Tanzania: An overview.

Malaria endemicity and epidemiology in Tanzania is changing rapidly as a result of changes in climatological, topographical and vector related factors. Malaria is now prevalent in previously malaria free mountainous areas, such as Muheza, Lushoto, Babati, Hanang and Loliondo Districts where records show dramatic changes in the incidence of and endemicity of malaria in the past five decades. The observed malaria epidemics in Tanzania were also greatly enhanced by a rapid increase in immigrants into and/or from malarious areas and by deforestation. Changes in mosquito host-preference, increased human socio-economic activities, and the wide self medication practices and drug resistance are also likely to have played important roles in malaria epidemics in Tanzania. This overview explores and discusses the contribution of the above-mentioned factors to malaria epidemics in the past five decades.