Hellen Gelband

Cancer Control Opportunities in Low- and Middle-Income Countries

Cancer is low or absent on the health agendas of low- and middle-income countries (LMCs) despite the fact that more people die from cancer in these countries than from AIDS and malaria combined. International health organizations, bilateral aid agencies, and major foundations—which are instrumental in setting health priorities—also have largely ignored cancer in these countries. This book identifies feasible, affordable steps for LMCs and their international partners to begin to reduce the cancer burden for current and future generations. Stemming the growth of cigarette smoking tops the list to prevent cancer and all the other major chronic diseases. Other priorities include infant vaccination against the hepatitis B virus to prevent liver cancers and vaccination to prevent cervical cancer. Developing and increasing capacity for cancer screening and treatment of highly curable cancers (including most childhood malignancies) can be accomplished using resource-level appropriateness as a guide. And there are ways to make inexpensive oral morphine available to ease the pain of the many who will still die from cancer.

Vaccines for preventing malaria

BACKGROUNDnDespite continued efforts to control the disease, malaria remains a major health problem in many regions of the world, especially sub-Saharan Africa, and new ways to control or eradicate the disease are urgently needed. Two types of vaccine, SPf66 vaccine against the asexual stages, and NANP vaccines against the sporozoite stages of the Plasmodium parasite, have been tested in randomised clinical trials in endemic areas.nnnOBJECTIVESnTo assess the effects of malaria vaccines.nnnSEARCH STRATEGYnThe Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles were searched. Organisations and researchers in the field were contacted.nnnSELECTION CRITERIAnRandomised trials comparing vaccines against Plasmodium falciparum, P. vivax, P. malariae or P. ovale, and placebo.nnnDATA COLLECTION AND ANALYSISnTwo independent reviewers assessed trial quality and conducted data extraction.nnnMAIN RESULTSnThirteen efficacy trials involving about 7700 people were included. There were nine trials of the Spf66 vaccine and four trials of the NANP vaccines. There was large heterogeneity between trials when investigating the effect of SPf66 in reducing incidence of the first attack of P. falciparum malaria. When trials were subcategorised by location, there was no evidence for effect of SPf66 in reducing incidence of P. falciparum in four African trials conducted in children under 5 years of age (Peto odds ratio [OR] = 0.96, 95% confidence interval [CI] 0.81 to 1.14). In five trials outside Africa with participants aged 2 years to adult, there was a reduction in incidence by SPf66 vaccine (Peto OR = 0.77, 95% CI 0.67 to 0.88, fixed effects model). Significant heterogeneity remained between trials conducted outside Africa. Using a random effects model for these five trials, the OR was 0.74 (95% CI 0.54 to 1.01). In five trials, there was no evidence for effect of the SPf66 vaccine on the incidence of the first attack of P. vivax malaria (OR 1.01, 95% CI 0.87 to 1.17). Trials to date have not indicated any severe adverse effects of SPf66 vaccine. In three trials of NANP-based vaccines, there was no evidence for protection by these vaccines against P. falciparum malaria (OR 1.12, 95% CI 0.64 to 1.93).nnnREVIEWERS CONCLUSIONSnThere is no evidence for protection by SPf66 vaccines against P. falciparum in Africa. There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in other regions. Further research with SPf66 vaccines in South America may be justified. Trials to date have not been of sufficient size to evaluate the effect of malaria vaccines on mortality or on severe malaria requiring admission to hospital. There was not enough evidence to evaluate the use of NANP vaccines.

Vaccines for preventing malaria (SPf66)

BACKGROUNDnA malaria vaccine is badly needed. SPf66 was one of the earliest vaccines developed. It is a synthetic peptide vaccine containing antigens from the blood stages of malaria linked together with an antigen from the sporozoite stage, and is targeted mainly against the blood (asexual) stages.nnnOBJECTIVESnTo assess the effect of SPf66 malaria vaccines against Plasmodium falciparum, P. vivax, P. malariae, and P. ovale in preventing infection, disease, and death.nnnSEARCH STRATEGYnWe searched the Cochrane Infectious Diseases Group Specialized Register (September 2005), CENTRAL (The Cochrane Library 2005, Issue 3), MEDLINE (1966 to September 2005), EMBASE (1980 to September 2005), LILACS (1982 to September 2005), Science Citation Index (1981 to September 2005), and reference lists of articles. We also contacted organizations and researchers in the field.nnnSELECTION CRITERIAnRandomized and quasi-randomized controlled trials comparing SPf66 vaccine with placebo or routine antimalarial control measures in people of any age receiving an artificial challenge or natural exposure to malaria infection (any species).nnnDATA COLLECTION AND ANALYSISnTwo people independently assessed trial quality and extracted data, including adverse events. Results were expressed as relative risks (RR) with 95% confidence intervals (CI).nnnMAIN RESULTSnTen efficacy trials of SPf66 involving 9698 participants were included. Results with SPf66 in reducing new episodes of P. falciparum malaria were heterogeneous: it was not effective in four African trials (RR 0.98, 95% CI 0.90 to 1.07; 2371 participants) or in one Asian trial (RR 1.06, 95% CI 0.90 to 1.25; 1221 participants). In four trials in South America the number of first attacks with P. falciparum was reduced by 28% (RR 0.72, 95% CI 0.63 to 0.82; 3807 participants). It did not reduce episodes of P. vivax malaria or admission to hospital with severe malaria. Trials have not indicated any serious adverse events with SPf66 vaccine.nnnAUTHORS CONCLUSIONSnThere is no evidence for protection by SPf66 vaccines against P. falciparum in Africa. There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in South America. There is no justification for further trials of SPf66 in its current formulation. Further research with SPf66 vaccines in South America or with new formulations of SPf66 may be justified.

Costs, affordability, and feasibility of an essential package of cancer control interventions in low-income and middle-income countries: key messages from Disease Control Priorities, 3rd edition

Investments in cancer control--prevention, detection, diagnosis, surgery, other treatment, and palliative care--are increasingly needed in low-income and particularly in middle-income countries, where most of the worlds cancer deaths occur without treatment or palliation. To help countries expand locally appropriate services, Cancer (the third volume of nine in Disease Control Priorities, 3rd edition) developed an essential package of potentially cost-effective measures for countries to consider and adapt. Interventions included in the package are: prevention of tobacco-related cancer and virus-related liver and cervical cancers; diagnosis and treatment of early breast cancer, cervical cancer, and selected childhood cancers; and widespread availability of palliative care, including opioids. These interventions would cost an additional US

Albendazole for the control and elimination of lymphatic filariasis: systematic review.

20 billion per year worldwide, constituting 3% of total public spending on health in low-income and middle-income countries. With implementation of an appropriately tailored package, most countries could substantially reduce suffering and premature death from cancer before 2030, with even greater improvements in later decades.

Vaccines for preventing malaria (blood‐stage)

Objectivesu2002 The Global Programme to Eliminate Lymphatic Filariasis recommends albendazole in combination with other antifilarial drugs. This systematic review examines albendazole in treatment and control of lymphatic filariasis.

Regimens of less than six months for treating tuberculosis

BACKGROUNDnA malaria vaccine is needed because of the heavy burden of mortality and morbidity due to this disease. This review describes the results of trials of blood (asexual)-stage vaccines. Several are under development, but only one (MSP/RESA, also known as Combination B) has been tested in randomized controlled trials.nnnOBJECTIVESnTo assess the effect of blood-stage malaria vaccines in preventing infection, disease, and death.nnnSEARCH STRATEGYnIn March 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE, EMBASE, LILACS, and the Science Citation Index. We also searched conference proceedings and reference lists of articles, and contacted organizations and researchers in the field.nnnSELECTION CRITERIAnRandomized controlled trials comparing blood-stage vaccines (other than SPf66) against P. falciparum, P. vivax, P. malariae, or P. ovale with placebo, control vaccine, or routine antimalarial control measures in people of any age receiving a challenge malaria infection.nnnDATA COLLECTION AND ANALYSISnBoth authors independently assessed trial quality and extracted data. Results for dichotomous data were expressed as relative risks (RR) with 95% confidence intervals (CI).nnnMAIN RESULTSnFive trials of MSP/RESA vaccine with 217 participants were included; all five reported on safety, and two on efficacy. No severe or systemic adverse effects were reported at doses of 13 to 15 microg of each antigen (39 to 45 microg total). One small efficacy trial with 17 non-immune participants with blood-stage parasites showed no reduction or delay in parasite growth rates after artificial challenge. In the second efficacy trial in 120 children aged five to nine years in Papua New Guinea, episodes of clinical malaria were not reduced, but MSP/RESA significantly reduced parasite density only in children who had not been pretreated with an antimalarial drug (sulfadoxine-pyrimethamine). Infections with the 3D7 parasite subtype of MSP2 (the variant included in the vaccine) were reduced (RR 0.38, 95% CI 0.26 to 0.57; 719 participants) while those with the other main subtype, FC27, were not (720 participants).nnnAUTHORS CONCLUSIONSnThe MSP/RESA (Combination B) vaccine shows promise as a way to reduce the severity of malaria episodes, but the effect of the vaccine is MSP2 variant-specific. Pretreatment for malaria during a vaccine trial makes the results difficult to interpret, particularly with the relatively small sample sizes of early trials. The results show that blood-stage vaccines may play a role and merit further development.

The SPf66 Malaria Vaccine: What is the Evidence for Efficacy?

BACKGROUNDnWHO recommends 6 months of treatment in TB programmes.nnnOBJECTIVESnThe purpose of this review is to assess the effects of regimens lasting less than 6 months compared with longer regimens in the treatment of active TB.nnnSEARCH STRATEGYnSearch strategy: MEDLINE 1955-, Cochrane Infectious Diseases Trials Register, existing reviews, and researchers in the field. Date of the most recent search: January 1999.nnnSELECTION CRITERIAnRandomized trials comparing two or more TB drug regimens, in which at least one regimen was <6 months and it was compared with at least one regimen that lasted longer, in any patients with active TB.nnnDATA COLLECTION AND ANALYSISnOne reviewer extracted data and assessed trial quality.nnnMAIN RESULTSnSeven trials with a total of 9 comparisons of <6 months (range: 2-5 months) versus longer treatment were included. About 2200 patients were in the shorter regimens and about 1900 in the longer regimens (the same comparison groups were used for more than one shorter regimen, in two studies). Relapse rates were consistently higher after shorter duration treatment regimens, regardless of the comparison made, though they were all relatively low. Results were significantly better in the longer groups in the meta-analyses of 2, 3, and 4 months of treatment vs longer treatment (Peto OR = 6.1 [95%CI 2.19,17.01], 3.67 [2.42,5.58], 3.64 [1.71,7. 75] but not in the single trial of 5 vs. 7 months (Peto OR = 2.24 [0. 90,5.59]. Relapse rates after longer (comparison) regimens ranged from 0-7% at one year (or more), and in the shorter treatment arms, they ranged from 1-9% in 8 trials, and18% relapsed in the one remaining. There was little or no difference in the rates of adverse reactions or toxicity requiring a change of regimen or discontinuation of treatment. The sterilizing efficacy at the end of treatment varied little among treatments, providing no predictive value for relapse rates. Few or no deaths were reported in the individual trials, and in no case did enough deaths occur for a comparison of short vs. long regimens.nnnREVIEWERS CONCLUSIONSnLonger periods of treatment (at least up to 6 months) result in higher success rates in patients with active TB, but the differences are small. Under field conditions, where adherence to treatment is a big problem, and shorter regimens might improve adherence, these differences may not be evident. A comparison of <6 months vs. 6 months of treatment under programme conditions would be needed to determine this.

Vaccines for preventing malaria (pre-erythrocytic)

This review was supported through a grant to the Effective Health Care in Developing Countries Project by the Department for International Development (UK) and the European Union (DG XII). However, DFID and EU accept no responsibility for any information provided or views expressed.

Primaquine or other 8‐aminoquinoline for reducing Plasmodium falciparum transmission

BACKGROUNDnVaccines against all stages of the malaria parasite are in development, mainly for Plasmodium falciparum, which causes the most serious form of malaria. Pre-erythrocytic vaccines act to prevent or delay a malaria attack by attacking the sporozoite and liver stages before the parasite reaches the bloodstream.nnnOBJECTIVESnTo assess the efficacy and safety of pre-erythrocytic malaria vaccines against any type of human malaria.nnnSEARCH STRATEGYnIn March 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE, EMBASE, LILACS, and the Science Citation Index. We also searched conference proceedings and reference lists of articles, and contacted organizations and researchers in the field.nnnSELECTION CRITERIAnRandomized controlled trials comparing pre-erythrocytic vaccines with placebo, control vaccine, or routine antimalarial control measures in people of any age receiving an artificial challenge or natural exposure to malaria infection.nnnDATA COLLECTION AND ANALYSISnBoth authors independently assessed trial quality and extracted data. Results of meta-analyses were expressed as relative risks with 95% confidence intervals (CI) using an intention-to-treat analysis.nnnMAIN RESULTSnNine safety and efficacy trials, and two safety trials, with over 3000 participants were included. In semi-immune children, RTS,S vaccine reduced clinical episodes of malaria by 26% (95% CI 13% to 37%) and severe malaria by 58% (95% CI 15% to 79%) for up to 18 months. Prevalence of parasitaemia was also reduced by 26% (95% CI 11% to 38%) at six months after immunization. RTS,S also reduced clinical malaria episodes by 63% (95% CI 18% to 83%) in semi-immune adult men in the second year of follow up after a booster dose. No severe adverse events were judged to be related to RTS,S vaccine, although the frequencies of injection site pain, swelling, arm motion limitation, headache, and malaise were increased in the vaccine groups. There was no evidence for effect of the CS-NANP vaccines (307 participants, 3 trials), CS102 peptide vaccine (14 participants, 1 trial), or the ME-TRAP vaccine (372 participants, 1 trial).nnnAUTHORS CONCLUSIONSnRTS,S vaccine was effective in preventing a significant number of clinical malaria episodes, including good protection against severe malaria in children for 18 months. No severe adverse events were attributable to the vaccine. Progression of this vaccine towards licensing is justified while efforts to increase its efficacy continue. The other vaccines do not look promising and further research is a priority.