Correction: Onchocerciasis: Target product profiles of in vitro diagnostics to support onchocerciasis elimination mapping and mass drug administration stopping decisions.

[This corrects the article DOI: 10.1371/journal.pntd.0010682.].

Identification of the onchocerciasis vector in the Kakoi-Koda focus of the Democratic Republic of Congo.

BACKGROUND: The objective of this study was to characterise the vector in a small hyper-endemic focus of onchocerciasis (the Kakoi-Koda focus) which has recently been discovered on the western slopes of the rift valley above Lake Albert. METHODOLOGY/PRINCIPAL FINDINGS: Aquatic stages of blackflies were collected by hand from streams and rivers, and anthropophilic adult females were collected by human landing catches. Using a combination of morphotaxonomy and DNA barcoding, the blackflies collected biting humans within the focus were identified as Simulium dentulosum and Simulium vorax, which were also found breeding in local streams and rivers. Simulium damnosum s.l., Simulium neavei and Simulium albivirgulatum were not found (except for a single site in 2009 where crabs were carrying S. neavei). Anthropophilic specimens from the focus were screened for Onchocerca DNA using discriminant qualitative real-time triplex PCR. One specimen of S. vorax was positive for Onchocerca volvulus in the body, and out of 155 S. dentulosum, 30% and 11% were infected and infective (respectively). CONCLUSIONS/SIGNIFICANCE: Simulium dentulosum currently appears to be the main vector of human onchocerciasis within the Kakoi-Koda focus, and S. vorax may be a secondary vector. It remains possible that S. neavei was the main (or only) vector in the past having now become rare as a result of the removal of tree-cover and land-use changes. Simulium vorax has previously been shown to support the development of O. volvulus in the laboratory, but this is the first time that S. dentulosum has been implicated as a probable vector of onchocerciasis, and this raises the possibility that other blackfly species which are not generally considered to be anthropophilic vectors might become vectors under suitable conditions. Because S. dentulosum is not a vector in endemic areas surrounding the Kakoi-Koda focus, it is probable that the Kakoi-Koda focus is significantly isolated.

Onchocerciasis: Target product profiles of in vitro diagnostics to support onchocerciasis elimination mapping and mass drug administration stopping decisions.

In June 2021, the World Health Organization (WHO), recognizing the need for new diagnostics to support the control and elimination of onchocerciasis, published the target product profiles (TPPs) of new tests that would support the two most immediate needs: (a) mapping onchocerciasis in areas of low prevalence and (b) deciding when to stop mass drug administration programs. In both instances, the test should ideally detect an antigen specific for live, adult O. volvulus female worms. The preferred format is a field-deployable rapid test. For mapping, the test needs to be ≥ 60% sensitive and ≥ 99.8% specific, while to support stopping decisions, the test must be ≥ 89% sensitive and ≥ 99.8% specific. The requirement for extremely high specificity is dictated by the need to detect with sufficient statistical confidence the low seroprevalence threshold set by WHO. Surveys designed to detect a 1-2% prevalence of a given biomarker, as is the case here, cannot tolerate more than 0.2% of false-positives. Otherwise, the background noise would drown out the signal. It is recognized that reaching and demonstrating such a stringent specificity criterion will be challenging, but test developers can expect to be assisted by national governments and implementing partners for adequately powered field validation.

Onchocerciasis Elimination: Progress and Challenges.

Onchocerciasis is a parasitic infection caused by the filarial nematode Onchocerca volvulus and transmitted through the bites of black flies of the genus Similium that breed in rivers and streams. The impact of mass treatment with ivermectin and supplemented by vector control in some countries has changed the global scene of onchocerciasis. There has been reported progress made in elimination of onchocerciasis in central and southern American countries and in some localities in Africa. The target for elimination in the Americas has been set at 2022 while for 12 countries in Africa this is expected in 2030. This review was conducted to examine the current status of onchocerciasis elimination at the global level and report on progress made. Literature searches were made through PubMed, articles in English or English abstracts, reports and any other relevant articles related to the subject. The global burden of onchocerciasis is progressively reducing and is no longer a public health problem in some regions. However, programs are challenged with a range of issues: cross-border transmission, diagnostic tools, Loa loa co-endemicity, limited workforce in entomology and maintaining enthusiasm among community drug distributors. More concerted effort using appropriate tools is required to overcome the challenges.

Elimination of Simulium neavei-Transmitted Onchocerciasis in Wambabya-Rwamarongo Focus of Western Uganda.

Wambabya-Rwamarongo onchocerciasis focus is one of the eight foci Uganda verified using the WHO verification guidelines. The approach for elimination was twice yearly treatment with ivermectin for every round, treating at least 90% of all the eligible population. This was in combination with vector elimination using Abate® (BASF SE, Limburgerhof, Germany) since elimination nationwide policy was launched. From 2008 to 2013, the program distributed ivermectin with a mean treatment coverage of the ultimate treatment goal (UTG) or eligible population of 91.2%, with a range of 85-96%. In 2009, vector elimination based on ground larviciding had a dramatic impact on the Simulium vectors, as the last fly was observed in October 2009. No more Simulium vectors were observed during a period of at least 7 years, including the 3-year posttreatment surveillance (PTS) until the focus was reclassified as eliminated in August 2017. During the PTS period, none of the 10,578 trapped crabs were found infested with the aquatic stages of the vector. The last infested crab was observed in March 2010, and for at least 7 years, no infested crabs were observed. Serological surveys showed that of 2,978 young children examined in 2013, only one was OV16 positive (0.0%; 95% CI: 0-0.21). In 2017, after the PTS period, all 3,079 young children examined were negative for OV16 (95% CI: 0-0.16). Therefore, entomological and serological results provided evidence that resulted in the reclassification of Wambabya-Rwamarongo focus from "transmission interrupted" to "transmission eliminated" with no possibility of recrudescence.

Historical Elimination of Onchocerciasis from Victoria Nile Focus in Central Uganda Verified Using WHO Criteria.

Uganda has verified elimination of seven onchocerciasis foci since 2007 when the nationwide onchocerciasis elimination policy was launched. However, the Victoria Nile focus (which was eliminated in the early 1970s) had not been verified. The objective of this study was to verify this focus to the WHO verification guidelines and bring it in line with recently eliminated foci. Vector control with dichlorodiphenyltrichloroethane was the main intervention used at the Victoria Nile from the 1950s to the 1970s. Historical fly collection sites along River Nile were identified for recent fly collection. Relevant health workers near the sites were trained to supervise fly collection activity. With support from communities, fly collectors were identified, trained, and equipped to collect Simulium flies for at least a year. A total of 854 Simulium flies were collected and analyzed by polymerase chain reaction to detect Onchocerca volvulus DNA. The communities and their leaders provided consent for the collection of dry blood spots (DBS) from children younger than 10 years for investigation of recent exposure to the disease. A total of 2,953 DBS were collected and analyzed by OV16 ELISA to detect the presence of IgG4 antibodies recognizing the OV16 antigen. The results showed that none of the flies carried O. volvulus DNA. Similarly, all the children were OV16 negative, showing no exposure to onchocerciasis. All the flies collected were identified as Simulium adersi, which is not a known vector for O. volvulus. The results confirmed that onchocerciasis and its vector Simulium damnosum had been eliminated in the Victoria Nile focus.

Two-year longitudinal survey reveals high genetic diversity of Schistosoma mansoni with adult worms surviving praziquantel treatment at the start of mass drug administration in Uganda.

BACKGROUND: A key component of schistosomiasis control is mass drug administration with praziquantel. While control interventions have been successful in several endemic regions, mass drug administration has been less effective in others. Here we focus on the impact of repeated praziquantel treatment on the population structure and genetic diversity of Schistosoma mansoni. METHODS: We examined S. mansoni epidemiology, population genetics, and variation in praziquantel susceptibility in parasites isolated from children across three primary schools in a high endemicity region at the onset of the Ugandan National Control Programme. Children were sampled at 11 timepoints over two years, including one week and four weeks post-praziquantel treatment to evaluate short-term impacts on clearance and evidence of natural variation in susceptibility to praziquantel. RESULTS: Prevalence of S. mansoni was 85% at baseline. A total of 3576 miracidia larval parasites, isolated from 203 individual children, were genotyped at seven loci. Overall, genetic diversity was high and there was low genetic differentiation, indicating high rates of parasite gene flow. Schistosome siblings were found both pre-treatment and four weeks post-treatment, demonstrating adult worms surviving treatment and natural praziquantel susceptibility variation in these populations at the beginning of mass drug administration. However, we did not find evidence for selection on these parasites. While genetic diversity decreased in the short-term (four weeks post-treatment), diversity did not decrease over the entire period despite four rounds of mass treatment. Furthermore, within-host genetic diversity was affected by host age, host sex, infection intensity and recent praziquantel treatment. CONCLUSIONS: Our findings suggest that praziquantel treatments have short-term impacts on these parasite populations but impacts were transient and no long-term reduction in genetic diversity was observed. High gene flow reduces the likelihood of local adaptation, so even though parasites surviving treatment were observed, these were likely to be diluted at the beginning of the Ugandan National Control Programme. Together, these results suggest that MDA in isolation may be insufficient to reduce schistosome populations in regions with high genetic diversity and gene flow.

The positive influence the Onchocerciasis Elimination Program for the Americas has had on Africa programs.

A recent article "Is onchocerciasis elimination in Africa feasible by 2025: a perspective based on lessons learnt from the African control programmes" in Infectious Diseases of Poverty claimed that undue influence on African programs by concepts developed by the Onchocerciasis Elimination Program of the Americas (OEPA) is detrimental to stopping mass drug administration (MDA) in Africa. This claim is made despite a record year for MDA stoppage in four African countries of > 3.5 million treatments in 2018, far exceeding any past OEPA or African Program for Onchocerciasis Control (APOC) stop MDA success.

Epidemiological description of a protracted cholera outbreak in Tonj East and Tonj North counties, former Warrap State, South Sudan, May-Oct 2017.

BACKGROUND: On 18th May 2017, State Ministry of Health of former Warrap State received a report from Tonj East County of an outbreak of acute watery diarrhoea and vomiting in Makuac payam. We conducted this investigation to confirm the causative organism and describe the epidemiology of the outbreak in order to support evidence-based control measures. METHODS: We defined a suspected case as a resident of Tonj East or Tonj North County with sudden onset of acute watery diarrhoea and vomiting between May 1 and October 15, 2017. A probable case was defined as a suspected case with a positive rapid test for Vibrio cholerae; a confirmed case was a probable case with a positive stool culture for V. cholerae. We conducted systematic case finding by visiting health facilities and villages in the affected payams. We reviewed patient records from 1 May 2017 to 15 October 2017, to identify suspected cholera case-patients. We conducted a descriptive epidemiologic study, examining the distribution of the cases. We computed the attack rates by age, sex, and payam of residence. Case fatality rate was calculated as the ratio of the total number of suspected cholera death to the total number of cholera case-patients. We conducted an oral cholera vaccination campaign after the peak of the outbreak to control and prevent the spread to other payams. RESULTS: We identified 1451 suspected cholera cases between May and October 2017. Of these, 81% (21/26) had a positive rapid diagnostic test for V. cholerae; out of the 16 rectal swabs transported to the National Public Laboratory, 88% (14/16) were confirmed to be V. cholerae O1 serotype Inaba. The epidemic curve shows continuous common source outbreak with several peaks. The mean age of the case-patients was 24 years (Range: 0.2-75y). The clinical presentations of the case-patients were consistent with cholera. Males had an attack rate of 9.9/10000. The highest attack rate was in ≥30y (14 per 10,000). Among the six payams affected, Makuac had the highest attack rate of 3/100. The case fatality rate (CFR) was 3.0% (44/1451). Paliang and Wunlit had an oral cholera vaccination coverage of ≥100%, while 4 payams had a vaccination coverage of < 90%. CONCLUSION: This was a continuous common source cholera outbreak caused by V. cholerae 01 sero type Inaba. We recommended strengthening of the surveillance system to improve early detection and effective response.

Operational Performance of the Onchocerca volvulus "OEPA" Ov16 ELISA Serological Assay in Mapping, Guiding Decisions to Stop Mass Drug Administration, and Posttreatment Surveillance Surveys.

Onchocerciasis is a neglected tropical disease targeted for elimination. The World Health Organization (WHO) has developed guidelines for the verification of onchocerciasis elimination that include entomological and epidemiological criteria. The latter require demonstrating with statistical confidence that the infection prevalence in children is less than 0.1%, necessitating an assay with a high degree of specificity. We present an analysis of the performance of the Onchocerciasis Elimination Program for the Americas (OEPA) version of the Ov16 enzyme-linked immunosorbant assay (ELISA) when used under operational conditions. In Africa and Latin America, the assay demonstrated 99.98% specificity in 69,888 children in 20 foci where transmission was believed to be interrupted. The assay produced a prevalence estimate equal to that of skin snip microscopy when applied in putatively hypo-endemic zones of Ethiopia. The OEPA Ov16 ELISA demonstrated the specificity required to be effectively deployed to verify transmission elimination under the WHO guidelines, while exhibiting a sensitivity equivalent to skin snip microscopy to identify hypo-endemic areas.

Insecticide resistance status of the malaria mosquitoes: Anopheles gambiae and Anopheles funestus in eastern and northern Uganda.

BACKGROUND: Uganda's malaria burden includes the sixth highest number of annual deaths in Africa (10,500) with approximately 16 million cases (2013) and the entire population at risk. The President's Malaria Initiative has been supporting the malaria control interventions of indoor residual spraying (IRS) and distribution of long-lasting insecticidal nets (LLIN) in Uganda since 2007. These interventions are threatened by emerging and spreading insecticide resistance, known to exist in Ugandan malaria vectors. Pyrethroid insecticides have been used in agriculture since the early 1990s and in IRS programmes from the mid-2000s until 2010. A universal LLIN coverage campaign was executed in 2013-2014, distributing pyrethroid-treated LLINs throughout the country. This study investigated insecticide susceptibility, intensity, and oxidase detoxification in Anopheles gambiae sensu lato and Anopheles funestus to permethrin and deltamethrin in four eastern Ugandan sites. METHODS: The susceptibility status of An. gambiae and An. funestus to bendiocarb, permethrin and deltamethrin was determined using the CDC (Centers for Disease Control and Prevention) bottle bioassay. Presence of oxidative enzyme detoxification mechanisms were determined by pre-exposing mosquitoes to piperonyl butoxide followed with exposure to discriminating doses of deltamethrin- and permethrin-coated CDC bottles. Resistance intensity was investigated using serial dosages of 1×, 2×, 5× and 10× the diagnostic dose and scored at 30 min to determine the magnitude of resistance to both of these LLIN pyrethroids. Testing occurred in the Northern and Eastern Regions of Uganda. RESULTS: Anopheles gambiae and An. funestus were fully susceptible to bendiocarb where tested. Anopheles gambiae resistance to deltamethrin and permethrin was observed in all four study sites. Anopheles funestus was resistant to deltamethrin and permethrin in Soroti. Oxidative resistance mechanisms were found in An. gambiae conferring pyrethroid resistance in Lira and Apac. 14.3% of An. gambiae from Tororo survived exposure of 10× concentrations of permethrin. CONCLUSIONS: Both An. gambiae and An. funestus are resistant to pyrethroids but fully susceptible to bendiocarb at all sites. Susceptibility monitoring guided the Ministry of Health's decision to rotate between IRS insecticide classes. Intensity bioassay results may indicate encroaching control failure of pyrethroid-treated LLINs and should inform decision-makers when choosing LLINs for the country.

Investigating a cholera outbreak in Kaiso Fishing Village, Hoima District, Uganda, October 2015.

Globally, even though improvements have been made to effective surveillance and response, communicable diseases such as cholera remain high priorities for national health programs, especially in Africa. High-quality surveillance information coupled with adequate laboratory facilities are effective in curbing outbreaks from such diseases, ultimately reducing morbidity and mortality. One way of building this capacity is through simulation of response to such health events. This case study based on a cholera outbreak investigated by FETP trainees in October 2015 in Uganda can be used to reinforce skills of frontline FETP trainees and other novice public health practitioners through a practical simulation approach. This activity should be completed in 2.5 hours.

The interruption of Onchocerca volvulus and Wuchereria bancrofti transmission by integrated chemotherapy in the Obongi focus, North Western Uganda.

INTERVENTION: Few studies have documented the interruption of onchocerciasis and Lymphatic Filariasis (LF) by integrated chemotherapy in Uganda. The study describes the interruption of transmission of the two diseases co-endemic in Obongi focus, north western Uganda. Base line data for Onchocerciasis and LF were collected in 1994 and 2006, respectively. Annual mass drug administration for onchocerciasis (Ivermectin) and Lymphatic Filariasis (Ivermectin + albendazole) was conducted for 20 and 6 years, respectively. Thereafter, assessments by skin snip, larval searches in rivers and human landing catches were performed. Children <10 years were screened for IgG4 antibodies using Ov16 ELISA technique in 2013. LF Pre-TAS and TAS1 were conducted in sentinel sites. ITN coverage and utilization for the implementation unit was also reported. INTERVENTION COVERAGE: Onchocerciasis treatment coverage was <80% but improved with the introduction of CDTI in 1999. While for LF, effective coverage of >65% was achieved in the six treatment rounds. Household ownership of ITN's and utilization was 96% and 72.4%., respectively. IMPACT: Parasitological examinations conducted for onchocerciasis among 807 adults and children, revealed a reduction in mf prevalence from 58% in 1994 to 0% in 2012. Entomological monitoring conducted at the two sites had no single Simulium damnosum fly caught. Serological analysis using Ov16 ELISA for onchocerciasis revealed that out of the 3,308 children <10 years old screened in 2013, only 3/3308 (0.091%) positive cases were detected. All Ov16 positive children were negative when tested for patent infection by skin snip PCR. A reduction in LF microfilaria prevalence from 2.5% (n = 13/522) in 2006 to 0.0% (n = 602) in 2014 was observed. LF TAS1 conducted in 2015 among 1,532 children 6-7 years, all were negative for antigens of W. bancrofti. CONCLUSION: The results concluded that interruption of onchocerciasis and LF has been achieved.

Cholera outbreak caused by drinking lake water contaminated with human faeces in Kaiso Village, Hoima District, Western Uganda, October 2015.

BACKGROUND: On 12 October 2015, a cholera outbreak involving 65 cases and two deaths was reported in a fishing village in Hoima District, Western Uganda. Despite initial response by the local health department, the outbreak persisted. We conducted an investigation to identify the source and mode of transmission, and recommend evidence-led interventions to control and prevent cholera outbreaks in this area. METHODS: We defined a suspected case as the onset of acute watery diarrhoea from 1 October to 2 November 2015 in a resident of Kaiso Village. A confirmed case was a suspected case who had Vibrio cholerae isolated from stool. We found cases by record review and active community case finding. We performed descriptive epidemiologic analysis for hypothesis generation. In an unmatched case-control study, we compared exposure histories of 61 cases and 126 controls randomly selected among asymptomatic village residents. We also conducted an environmental assessment and obtained meteorological data from a weather station. RESULTS: We identified 122 suspected cases, of which six were culture-confirmed, 47 were confirmed positive with a rapid diagnostic test and two died. The two deceased cases had onset of the disease on 2 October and 10 October, respectively. Heavy rainfall occurred on 7-11 October; a point-source outbreak occurred on 12-15 October, followed by continuous community transmission for two weeks. Village residents usually collected drinking water from three lakeshore points - A, B and C: 9.8% (6/61) of case-persons and 31% (39/126) of control-persons were found to usually use point A, 21% (13/61) of case-persons and 37% (46/126) of control-persons were found to usually use point B (OR = 1.8, 95% CI: 0.64-5.3), and 69% (42/61) of case-persons and 33% (41/126) of control-persons were found to usually use point C (OR = 6.7; 95% CI: 2.5-17) for water collection. All case-persons (61/61) and 93% (117/126) of control-persons reportedly never treated/boiled drinking water (OR = ∞, 95% CI Fisher: 1.0 - ∞). The village's piped water system had been vandalised and open defecation was common due to a lack of latrines. The lake water was found to be contiminated due to a gully channel that washed the faeces into the lake at point C. CONCLUSIONS: This outbreak was likely caused by drinking lake water contaminated by faeces from a gully channel. We recommend treatment of drinking water, fixing the vandalised piped-water system and constructing latrines.

Malaria incidence among children less than 5 years during and after cessation of indoor residual spraying in Northern Uganda.

BACKGROUND: In June 2015, a malaria epidemic was confirmed in ten districts of Northern Uganda; after cessation of indoor residual spraying (IRS). Epidemic was defined as an increase in incidence per month beyond one standard deviation above mean incidence of previous 5 years. Trends in malaria incidence among children-under-5-years were analysed so as to describe the extent of change in incidence prior to and after cessation of IRS. METHODS: Secondary data on out-patient malaria case numbers for children-under-5-years July 2012 to June 2015 was electronically extracted from the district health management information software2 (DHIS2) for ten districts that had IRS and ten control districts that didn't have IRS. Data was adjusted by reporting rates, cleaned by smoothing and interpolation and incidence of malaria per 1000 population derived. Population data obtained from 2002 and 2014 census reports. Data on interventions obtained from malaria programme reports, rainfall data obtained from Uganda National Meteorological Authority. Three groups of districts were created; two based on when IRS ended, the third not having IRS. Line graphs were plotted showing malaria incidence vis-à-vis implementation of IRS, mass net distribution and rainfall. Changes in incidence after withdrawal of IRS were obtained using incidence rate ratios (IRR). IRR was calculated as incidence for each month after the last IRS divided by incidence of the IRS month. Poisson regression was used to test statistical significance. RESULTS: Incidence of malaria declined between spray activities in districts that had IRS. Decline in IRR for 4 months after last IRS month was greater in the sprayed than control districts. On the seventh month following cessation of IRS, incidence in sprayed districts rose above that of the last spray month [1.74: 95% CI (1.40-2.15); and 1.26: 95% CI (1.05-1.51)]. Rise in IRR continued from 1.26 to 2.62 (95% CI 2.21-3.12) in June 2015 for districts that ended IRS in April 2014. Peak in rainfall occurred in May 2015. CONCLUSION: There was sustained control of malaria incidence during IRS implementation. Following withdrawal and peak in rainfall, incidence rose to epidemic proportions. This suggests a plausible link between the malaria epidemic, peak in rainfall and cessation of IRS.

Rapid reduction of malaria following introduction of vector control interventions in Tororo District, Uganda: a descriptive study.

BACKGROUND: In 2012, Tororo District had the highest malaria burden in Uganda with community Plasmodium prevalence of 48%. To control malaria in the district, the Ministry of Health introduced universal distribution of long lasting insecticide-treated nets (LLINs) in 2013 and added indoor residual spraying (IRS) in 2014. This study assessed malaria incidence, test positivity rates and outpatient (OPD) attendance due to malaria before and after vector control interventions. METHODS: This study was based on analysis of Health Management Information System (HMIS) secondary malaria surveillance data of 2,727,850 patient records in OPD registers of 61 health facilities from 2012 to 2015. The analysis estimated monthly malaria incidence for the entire population and also separately for <5- and ≥5-year-olds before and after introduction of vector control interventions; determined laboratory test positivity rates and annual percentage of malaria cases in OPD. Chi square for trends was used to analyse annual change in malaria incidence and logistic regression for monthly reduction. RESULTS: Following universal LLINs coverage, the annual mean monthly malaria incidence fell from 95 cases in 2013 to 76 cases per 1000 in 2014 with no significant monthly reduction (OR = 0.99, 95% CI 0.96-1.01, P = 0.37). Among children <5 years, the malaria incidence reduced from 130 to 100 cases per 1000 (OR = 0.98, 95% CI 0.97-1.00, P = 0.08) when LLINs were used alone in 2014, but declined to 45 per 1000 in 2015 when IRS was combined with LLINs (OR = 0.94, 95% CI 0.91-0.996, P < 0.0001). Among individuals aged ≥5 years, mean monthly malaria incidence reduced from 59 to 52 cases per 1000 (OR = 0.99, 95% CI 0.97-1.02, P = 0.8) when LLINs were used alone in 2014, but reduced significantly to 25 per 1000 in 2015 (OR = 0.91, 95% CI 0.88-0.94, P < 0.0001). Malaria test positivity rate reduced from 57% in 2013 to 30% (Chi = 15, P < 0.0001) in 2015. Slide positivity rate reduced from 45% in 2013 to 21% in 2015 (P = 0.004) while RDT positivity declined from 69 to 40%. CONCLUSIONS: A rapid reduction in malaria incidence was observed in Tororo District following the introduction of IRS in addition to LLINs. There was no significant reduction in malaria incidence following universal distribution of LLINs to communities before introduction of IRS.

A large and persistent outbreak of typhoid fever caused by consuming contaminated water and street-vended beverages: Kampala, Uganda, January - June 2015.

BACKGROUND: On 6 February 2015, Kampala city authorities alerted the Ugandan Ministry of Health of a "strange disease" that killed one person and sickened dozens. We conducted an epidemiologic investigation to identify the nature of the disease, mode of transmission, and risk factors to inform timely and effective control measures. METHODS: We defined a suspected case as onset of fever (≥37.5 °C) for more than 3 days with abdominal pain, headache, negative malaria test or failed anti-malaria treatment, and at least 2 of the following: diarrhea, nausea or vomiting, constipation, fatigue. A probable case was defined as a suspected case with a positive TUBEX® TF test. A confirmed case had blood culture yielding Salmonella Typhi. We conducted a case-control study to compare exposures of 33 suspected case-patients and 78 controls, and tested water and juice samples. RESULTS: From 17 February-12 June, we identified 10,230 suspected, 1038 probable, and 51 confirmed cases. Approximately 22.58% (7/31) of case-patients and 2.56% (2/78) of controls drank water sold in small plastic bags (ORM-H = 8.90; 95%CI = 1.60-49.00); 54.54% (18/33) of case-patients and 19.23% (15/78) of controls consumed locally-made drinks (ORM-H = 4.60; 95%CI: 1.90-11.00). All isolates were susceptible to ciprofloxacin and ceftriaxone. Water and juice samples exhibited evidence of fecal contamination. CONCLUSION: Contaminated water and street-vended beverages were likely vehicles of this outbreak. At our recommendation authorities closed unsafe water sources and supplied safe water to affected areas.

The Imaramagambo Onchocerciasis Focus in Southwestern Uganda: Interruption of Transmission After Disappearance of the Vector Simulium neavei and Its Associated Freshwater Crabs.

It was not until early 1990s that, when the Imaramagambo focus of southwest Uganda was mapped, mass treatment with a single annual dose of ivermectin for onchocerciaisis control commenced. However, comprehensive investigations on its transmission were launched after a nationwide policy for onchocerciasis elimination in 2007. Entomological surveys throughout the focus from 2007 to 2015 have yielded few or no freshwater crabs (Potamonautes aloysiisabaudiae), which serve as the obligate phoretic host of the larvae and pupae of the vector Simulium neavei No S. neavei flies have been observed or collected since 2007. Skin snips (microscopy) from 294 individuals in 2008 were negative for skin microfilariae, and of the 462 persons analyzed by polymerase chain reaction skin snip poolscreen in 2009, only five (1.08%) persons were indicated as infected with onchocerciasis. All five of the positive persons were at least 40 years old. Serosurvey results showed negative exposure among 3,332 children in 2012 and 3,108 children in 2015. Both were within the upper bound of the 95% confidence interval of the prevalence estimate of 0.06%, which confirmed the elimination of onchocerciasis. Treatment coverage in Imaramagambo was generally poor, and transmission interruption of onchocerciasis could not be attributed solely to annual mass treatment with ivermectin. There was sufficient evidence to believe that the possible disappearance of the S. neavei flies, presumed to have been the main vector, may have hastened the demise of onchocerciasis in this focus.