Moses Katabarwa

Serosurveillance to Monitor Onchocerciasis Elimination: The Ugandan Experience

Uganda is the only African country whose onchocerciasis elimination program uses a two-pronged approach of vector control and mass drug distribution. The Ugandan program relies heavily upon the use of serosurveys of children to monitor progress toward elimination. The program has tested over 39,000 individuals from 11 foci for Onchocerca volvulus exposure, using the Ov16 ELISA test. The data show that the Ov16 ELISA is a useful operational tool to monitor onchocerciasis transmission interruption in Africa at the World Health Organization (WHO) recommended threshold of < 0.1% in children. The Ugandan experience has also resulted in a re-examination of the statistical methods used to estimate the boundary of the upper 95% confidence interval for the WHO prevalence threshold when all samples tested are negative. This has resulted in the development of Bayesian and hypergeometric statistical methods that reduce the number of individuals who must be tested to meet the WHO criterion.

Community-directed interventions strategy enhances efficient and effective integration of health care delivery and development activities in rural disadvantaged communities of Uganda

The community‐directed interventions (CDI) strategy achieved a desired coverage of the ultimate treatment goal (UTG) of at least 90% with ivermectin distribution for onchocerciasis control, and filled the gap between the health care services and the communities. However, it was not clear how its primary actors – the community‐directed health workers (CDHW) and community‐directed health supervisors (CDHS) – would perform if they were given more responsibilities for other health and development activities within their communities. A total of 429 of 636 (67.5%) of the CDHWs who were involved in other health and development activities performed better than those who were involved only in ivermectin distribution, with a drop‐out rate of 2.3%. A total of 467 of 864 (54.1%) of CDHSs who were involved in other health and development activities also maintained the desired level of performance. They facilitated updating of household registers (P < 0.05), trained and supervised CDHWs, and educated community members about onchocerciasis control (P < 0.001). Their drop‐out rate was 2.6%. The study showed that the majority of those who dropped out had not been selected by their community members. Therefore, CDI strategy promoted integration of health and development activities with a high potential for sustainability.

Seventeen Years of Annual Distribution of Ivermectin Has Not Interrupted Onchocerciasis Transmission in North Region, Cameroon

We studied onchocerciasis transmission and impact on ocular morbidity in three health districts in North Region, Cameroon, where annual mass ivermectin treatment has been provided for 12-17 years. The studies, which took place from 2008 to 2010, consisted of skin snips for microfilariae (mf), palpation examinations for nodules, slit lamp examinations for mf in the eye, and Simulium vector dissections for larval infection rates. Adults had mf and nodule rates of 4.8% and 13.5%, respectively, and 5.5% had mf in the anterior chamber of the eye. Strong evidence of ongoing transmission was found in one health district, where despite 17 years of annual treatments, the annual transmission potential was 543 L3/person per year; additionally, children under 10 years of age had a 2.6% mf prevalence. Halting ivermectin treatments in North Cameroon now might risk recrudescence of transmission and ocular disease.

The disappearance of onchocerciasis from the Itwara focus, western Uganda after elimination of the vector Simulium neavei and 19 years of annual ivermectin treatments

The Itwara onchocerciasis focus is located around the Itwara forest reserve in western Uganda. In 1991, annual treatments with ivermectin started in the focus. They were supplemented in 1995 by the control of the vector Simulium neavei, which was subsequently eliminated from the focus. The impact of the two interventions on the disease was assessed in 2010 by nodule palpations, examinations of skin snips by microscopy and PCR, and Ov16 recombinant ELISA. There was no evidence of any microfilaria in 688 skin snips and only 2 (0.06%) of 3316 children examined for IgG4 were slightly above the arbitrary cut off of 40. A follow up of the same children 21 months later in 2012 confirmed that both were negative for diagnostic antigen Ov-16, skin snip microscopy and PCR. Based on the World Health Organization (WHO) elimination criteria of 2001 and the Uganda onchocerciasis certification guidelines, it was concluded that the disease has disappeared from the Itwara focus after 19 years of ivermectin treatments and the elimination of the vector around 2001. Ivermectin treatments were recommended to be halted.

Transmission of Onchocerca volvulus by Simulium neavei in Mount Elgon Focus of Eastern Uganda Has Been Interrupted

The study determined that Simulium neavei-transmitted onchocerciasis in Mount Elgon onchocerciasis focus had been interrupted. Annual mass treatment with ivermectin changed to two times per year along with vector elimination in 2007. Then, baseline microfilaria (mf) prevalence data of 1994 in five sentinel communities were compared with follow-up data in 2005 and 2011. Blood spots from 3,051 children obtained in 2009 were analyzed for Onchocerca volvulus immunoglobulin G4 antibodies. Fresh water crab host captures and blackflies collected indicated their infestation with larval stages of S. neavei and presence or absence of the vector, respectively. Mf rates dropped from 62.2% to 0.5%, and 1 (0.03%) of 3,051 children was positive for O. volvulus antibodies. Crab infestation dropped from 41.9% in 2007 to 0%, and S. neavei biting reduced to zero. Both remained zero for the next 3 years, confirming interruption of onchocerciasis transmission, and interventions were halted.

Factors affecting the attrition of community-directed distributors of ivermectin, in an onchocerciasis-control programme in the Imo and Abia states of south-eastern Nigeria.

Abstract In areas of Nigeria where onchocerciasis is endemic, community-directed distributors (CDD) distribute ivermectin annually, as part of the effort to control the disease. Unfortunately, it has been reported that at least 35% of the distributors who have been trained in Nigeria are unwilling to participate further as CDD. The selection and training of new CDD, to replace those unwilling to continue, leads to annual expense that the national onchocerciasis-programme is finding difficult to meet, given other programme priorities and the limited resources. If the reported levels of attrition are true, they seriously threaten the sustainability of community-directed treatment with ivermectin (CDTI) in Nigeria. In 2002, interviews were held with 101 people who had been trained as CDD, including those who had stopped serving their communities, from 12 communities in south–eastern Nigeria that had high rates of CDD attrition. The results showed that, although the overall reported CDD attrition was 40.6%, the actual rate was only 10.9%. The CDD who had ceased participating in the annual rounds of ivermectin blamed a lack of incentives (65.9%), the demands of other employment (14.6%), the long distances involved in the house-to-house distribution (12.2%) or marital duties (7.3%). Analysis of the data obtained from all the interviewed CDD showed that inadequate supplies of ivermectin (P<0.01), lack of supervision (P<0.05) and a lack of monetary incentives (P<0.001) led to significant increases in attrition. Conversely, CDD retention was significantly enhanced when the distributors were selected by their community members (P<0.001), supervised (P<0.001), supplied with adequate ivermectin tablets (P<0.05), involved in educating their community members (P<0.05), and/or involved in other health programmes (P<0.001). Although CDD who were involved in other health programmes were relatively unlikely to cease participating in the distributions, they were more likely to take longer than 14 days to complete ivermectin distribution than other CDD, who only distributed ivermectin. Data obtained in interviews with present and past CDD appear vital for informing, directing, protecting and enhancing the performance of CDTI programmes, in Nigeria and elsewhere.

Community-directed health (CDH) workers enhance the performance and sustainability of CDH programmes: experience from ivermectin distribution in Uganda

The performance and ‘drop-out’ rates of ivermectin (Mectizan®) distributors in the Ugandan programme for community-directed treatment with ivermectin (CDTI) were investigated and related to the manner in which the distributors were recruited. Distributors, from randomly selected communities endemic for onchocerciasis in seven of the 10 affected districts, were interviewed. Questionnaires were initially completed for 296 communities (in which ivermectin had been distributed in 1998 but not in 1999) and then extended to another 310 communities (in which ivermectin had been distributed in both study years). Discussions were also held with some other community members, in participatory evaluation meetings (PEM) in 14 communities from four districts. Despite the CDTI being labelled as ‘community-directed’, the first round of interviews and questionnaires revealed that there were in fact three categories of distributors: 322 (69.4%) of those questioned had been selected by community members and were therefore truly community-directed health workers (CDHW) but 101 (22%) were community-based health workers appointed by the leaders of the local council (CBHW-LC) and 41 (9%) were self-appointed volunteers (CBHW-SA). During 1999, only the CDHW received good community support; they still helped to mobilise and educate their community members and advocate CDTI, and 98% of them agreed that they would distribute ivermectin during the following year. In contrast, many of the CBHW-LC were neither supported nor appreciated by the community members. Presumably in consequence, many of the CBHW-LC did not help to mobilise or educate their community members in 1999, nor did they advocate CDTI. Almost all (95%) of the CBHW-LC said that they would not be available to distribute in the following year, and were therefore regarded as total ‘drop-outs’ from the CDTI. The CBHW-SA were better supported by community members than were the CBHW-LC, they did more to advocate the CDTI, and 93% reported that they would distribute ivermectin during the following year. The ‘drop-out’ rates for 1999 were < 2% for the CDHW, 7% for the CBHW-SA, and 95% for the CBHW-LC. The results also indicated that the CBHW-SA were not as reliable as the CDHW. Similar results were obtained from the second round of questionnaires, in which 224 (73%) of the interviewees were CDHW, 57 (18%) were CBHW-LC and 28 (9%) were CBHW-SA. The results of the PEM showed that the CDHW, who mainly came from the same kinship groups as the people who selected them, were likely to achieve higher ivermectin coverage within a week than the other categories of distributors. It is clear that, for the optimum performance and sustainability of the CDTI, the distributors used should be CDHW selected by their own community members.

Monitoring ivermectin distributors involved in integrated health care services through community-directed interventions: a comparison of Cameroon and Uganda experiences over a period of three years (2004-2006)

Objectives  To assess and compare the effectiveness of ivermectin distributors in attaining 90% treatment coverage of the eligible population with each additional health activity they take up.

Twice-yearly ivermectin for onchocerciasis: the time is now

www.thelancet.com/infection Vol 14 May 2014 373 That Chen and colleagues do not include these data high lights persistent deficiencies in dissemination of data from randomised controlled trials. These deficiencies are especially glaring in this case, because US taxpayers effectively subsidised the two trials. Acting under authority granted by the Best Pharmaceuticals for Children Act (BPCA), passed by the US Congress to address important gaps in knowledge about the effects of drugs in paediatric populations, the FDA specifi cally requested data from both trials (and the pharmacokinetic study) from 3M, then the drug’s manufacturer. In return, the FDA rewarded 3M with an additional 6 months of marketing exclusivity for imiquimod. Unfortunately, the BPCA does not require publication of study results. The two trials—like many BPCA studies—have not been published in medical journals. The public availability of the trial data in the prescribing information and on the FDA website has not translated to awareness in the medical community. Physicians, including those who write review articles, do not routinely search those sources. Indeed, until a colleague and I raised this issue in a recent article, no major review articles, textbook chapters, or online references included these trial findings. Even a 2009 systematic review by the Cochrane collaboration failed to capture the trial results in its search. As I and others have argued, the US Congress should amend the BPCA to require publication of study fi ndings. Physicians, including authors of reviews, should routinely search drug prescribing information and the FDA website for relevant information. The investigators who did the two trials of imiquimod and molluscum should publish the results showing lack of efficacy. Most importantly, physicians should stop recommending and prescribing imiquimod to treat molluscum contagiosum in children. I am a shareholder in Synta Pharmaceuticals Corp and Arrowhead Research Co. The views presented in this Correspondence are those of the author and do not necessarily represent the views of The Permanente Medical Group.

Transmission of Onchocerca volvulus Continues in Nyagak-Bondo Focus of Northwestern Uganda after 18 Years of a Single Dose of Annual Treatment with Ivermectin

The objective of the study was to determine whether annual ivermectin treatment in the Nyagak-Bondo onchocerciasis focus could safely be withdrawn. Baseline skin snip microfilariae (mf) and nodule prevalence data from six communities were compared with data collected in the 2011 follow-up in seven communities. Follow-up mf data in 607 adults and 145 children were compared with baseline (300 adults and 58 children). Flies collected in 2011 were dissected, and poolscreen analysis was applied to ascertain transmission. Nodule prevalence in adults dropped from 81.7% to 11.0% (P < 0.0001), and mf prevalence dropped from 97.0% to 23.2% (P < 0.0001). In children, mf prevalence decreased from 79.3% to 14.1% (P < 0.0001). Parous and infection rates of 401 flies that were dissected were 52.9% and 1.5%, respectively, whereas the infective rate on flies examination by polymerase chain reaction (PCR) was 1.92% and annual transmission potential was 26.9. Stopping ivermectin treatment may result in onchocerciasis recrudescence.