Introduction: Access to and the cost of induction treatment for cryptococcal meningitis (CM) is rapidly changing. The newly-announced price for flucytosine ($0.75 per 500 mg pill) and possibly lower prices for liposomal amphotericin B (AmB-L) create opportunities to reduce CM treatment costs compared to the current standard treatment in low- and middle-income countries. Methods: We developed an Excel-based cost model to estimate health system treatment costs for CM over a two-week induction phase for multiple treatment combinations, newly feasible with improved access to flucytosine and AmB-L. CM treatment costs include medications, laboratory tests and other hospital-based costs (bed-day costs and healthcare worker time). We report results from applying the model using country-specific information for South Africa, Uganda, Nigeria, and Botswana. Results: A 14-day induction-phase of seven days of inpatient AmB-D with flucytosine, followed by seven days of high-dose fluconazole as an outpatient, will cost health systems less than a 14-day hospital stay with AmB-D and fluconazole. If daily AmB-L replaces AmB-D for those with baseline renal dysfunction, with a cost of $50 or less per 50 mg vial, incremental costs would still be less than the AmB-D with fluconazole regimen. Simple oral combinations (e.g., seven days of flucytosine with fluconazole as an inpatient) are practical when AmB-D is not available, and treatment costs would remain less than the current standard treatment. Conclusions: Improved access to and lower prices for flucytosine and AmB-L create opportunities for improving CM treatment regimens. An induction regimen of flucytosine and AmB-D for seven days is less costly than standard care in the settings studied here. As this regimen has also been shown to be more effective than current standard care, countries should prioritize scaling up flucytosine access. The cost of AmB-L based regimens is highly dependent on the price of AmB-L, which currently remains unclear.

Histoplasma antigen can be detected in people with advanced HIV disease (AHD), allowing for early and accurate diagnosis of histoplasmosis. The aim of this analysis was to assess the cost-effectiveness of routine histoplasmosis screening using antigen detection, among people with AHD. We developed a decision analytic model to evaluate Histoplasma antigen screening among people with AHD. The model estimated the costs, effectiveness, and cost-effectiveness of routine screening for Histoplasma antigen compared to the current practice of no routine Histoplasma antigen screening. The model includes stratification by symptoms of histoplasmosis, severity of presentation, and estimates of 30-day mortality. Data sources were taken from the Pan American Health Organization (PAHO) Strategic Fund databases on public purchases of medicines, and published literature on treatment outcomes. Outcome measures are life years saved (LYS), costs (US dollars), and incremental cost-effectiveness ratios (ICERs). Routine Histoplasma antigen screening avoids an estimated 17% of deaths in persons with advanced HIV disease, and is cost-effective compared to no histoplasmosis screening, with an ICER of $26/LYS. In sensitivity analysis assuming treatment for histoplasmosis with liposomal amphotericin, Histoplasma antigen screening remains cost-effective with an ICER of $607/LYS. Histoplasma antigen screening among people with AHD is a cost-effective strategy and could potentially avert 17% of AIDS-related deaths. Prospective evaluation of histoplasmosis screening is warranted to determine effectiveness and treatment outcomes with this strategy.

Continuity of key water, sanitation, and hygiene (WASH) infrastructure and WASH practices-for example, hand hygiene-are among several critical community preventive and mitigation measures to reduce transmission of infectious diseases, including COVID-19 and other respiratory diseases. WASH guidance for COVID-19 prevention may combine existing WASH standards and new COVID-19 guidance. Many existing WASH tools can also be modified for targeted WASH assessments during the COVID-19 pandemic. We partnered with local organizations to develop and deploy tools to assess WASH conditions and practices and subsequently implement, monitor, and evaluate WASH interventions to mitigate COVID-19 in low- and middle-income countries in Latin America and the Caribbean and Africa, focusing on healthcare, community institution, and household settings and hand hygiene specifically. Employing mixed-methods assessments, we observed gaps in access to hand hygiene materials specifically despite most of those settings having access to improved, often onsite, water supplies. Across countries, adherence to hand hygiene among healthcare providers was about twice as high after patient contact compared to before patient contact. Poor or non-existent management of handwashing stations and alcohol-based hand rub (ABHR) was common, especially in community institutions. Markets and points of entry (internal or external border crossings) represent congregation spaces, critical for COVID-19 mitigation, where globally-recognized WASH standards are needed. Development, evaluation, deployment, and refinement of new and existing standards can help ensure WASH aspects of community mitigation efforts that remain accessible and functional to enable inclusive preventive behaviors.

BACKGROUND: The purpose of this systematic review is to provide updated evidence on the preferred induction therapy for the treatment of HIV-associated cryptococcal meningitis considering the most recent evidence available in order to inform the need for updates to WHO guidelines. METHODS: We searched Medline via PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov for published or completed randomized clinical trials that evaluated induction treatment of first episode HIV-associated cryptococcal meningitis from 9 July 2018 (date of last search) to 1 September 2021. RESULTS: One randomized clinical trial of 844 people with HIV-associated cryptococcal meningitis met the inclusion criteria. Participants were randomized to: (1) amphotericin deoxycholate for 7 days, with flucytosine and fluconazole (control); or (2) a single dose of liposomal amphotericin 10 mg/kg with flucytosine and fluconazole (intervention). In the intention-to-treat analysis, 10-week mortality was 24.8% [95% confidence interval (CI): 20.7-29.3%] in the single-dose liposomal amphotericin group compared with 28.7% (95% CI: 24.4-33.4%) in the control group. The absolute difference in 10-week mortality was -3.9% with an upper one-sided 95% CI of 1.2%, within the 10% pre-specified non-inferiority margin. Fewer participants had grade 3 and 4 adverse events in the intervention arm compared with the control arm (50.0% vs. 62.3%, p < 0.001). CONCLUSIONS: In the single study included in this systematic review, single high-dose liposomal amphotericin B with flucytosine and fluconazole was non-inferior to the WHO-recommended standard of care induction therapy for HIV-associated cryptococcal meningitis, with significantly fewer adverse events.

BACKGROUND: Cryptococcal meningitis is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. The estimates of national, regional, and global burden of cryptococcal meningitis are essential to guide prevention strategies and determine needs for diagnostic tests and treatments. We present a 2020 estimate of the global burden of HIV-associated cryptococcal infection (antigenaemia), cryptococcal meningitis, and cryptococcal-associated deaths. METHODS: We defined advanced HIV disease as adults with a CD4 count of less than 200 cells/μL, as this group is at highest risk for cryptococcosis. We used UNAIDS estimates (2019-20) and population-based HIV impact assessment surveys (2016-18) to estimate the number of adults with CD4 counts of less than 200 cells/μL at risk for cryptococcosis, by country and region. Secondly, we summarised cryptococcal antigenaemia prevalence in those with a CD4 count of less than 200 cells/μL by reviewing published literature. Thereafter, we calculated the number of cryptococcal antigen (CrAg)-positive people in each country and region by multiplying the number with advanced HIV disease at risk for cryptococcal infection by the cryptococcal antigenaemia prevalence of the respective country or region. We estimated progression from cryptococcal antigenaemia to meningitis or death based on estimates from the published literature. FINDINGS: We estimated that there were 4·3 million (IQR 3·0-4·8) adults with HIV and CD4 counts of less than 200 cells/μL globally in 2020. We calculated a mean global cryptococcal antigenaemia prevalence of 4·4% (95% CI 1·6-7·4) among HIV-positive people with CD4 counts of less than 200 cells/μL, corresponding to 179 000 cases (IQR 133 000-219 000) of cryptococcal antigenaemia globally in 2020. Annually, we estimated that there are 152 000 cases (111 000-185 000) of cryptococcal meningitis, resulting in 112 000 cryptococcal-related deaths (79 000-134 000). Globally, cryptococcal disease accounts for 19% (13-24) of AIDS-related mortality. INTERPRETATION: Despite a reduction in the estimated absolute global burden of HIV-associated cryptococcal meningitis compared with 2014, likely to be due to antiretroviral therapy expansion, cryptococcal disease still accounts for 19% of AIDS-related deaths, similar to 2014 estimates. To end cryptococcal meningitis deaths by 2030, cryptococcal diagnostics, meningitis treatments, and implementation of preventive screening are urgently needed. FUNDING: None.

Foodborne disease outbreak investigations identify foods responsible for illnesses. However, it is not known the degree to which foods implicated in outbreaks reflect the distribution of food consumption in the U.S. population or the risk associated with their consumption. To examine this, we compared the distribution of foods in 24 categories implicated in outbreaks to the distribution of foods consumed by the U.S. population. Beef, chicken, eggs, fish, herbs, mollusks, pork, sprouts, seeded vegetables, and turkey were implicated in outbreaks significantly more often than expected based on the frequency of their consumption in the general population, suggesting a higher risk of contamination or mishandling from foods in these categories than in others. In contrast, pasteurized dairy, fruits, grains-beans, oils and sugars, and root/underground vegetables were less frequently implicated in outbreaks than they were consumed in the general population, suggesting a lower risk for these food categories.

The UNAIDS target to reduce HIV-related death to fewer than 500 000 deaths per year by 2020 will not be met.1 This statement might not be headline grabbing as this target was never as prominent as the 90-90-90 targets,2 the achievement of which is a necessary but not sufficient step towards ending AIDS mortality. | | The decline in HIV-related deaths is too slow. Early initiation of antiretroviral therapy (ART) for people living with HIV is the most important intervention for reducing HIV-related deaths. Access to ART for all is a distant goal in some settings due to ongoing challenges in identifying people with HIV and getting them on to treatment1 and ART alone isn’t enough to fully address HIV-related deaths. Among adults and adolescents, advanced HIV disease is diagnosed as a CD4 count of fewer than 200 cells per μL or a WHO stage 3 or 4 event.3 Evidence from South Africa shows more advanced HIV disease among ART-experienced people than among ART-naive people.4 Efforts to prevent disease progression will never replace the need for parallel improvements in the treatment of opportunistic infections.

The Somali Region of Ethiopia has been affected by drought for several years. Drought conditions have led to food and water scarcity and a humanitarian crisis in the region. In January 2017, an outbreak of acute watery diarrhea (AWD) was declared in the region. AWD prevention and control activities include strengthening water, sanitation, and hygiene (WASH) services. Access to safe drinking water is critical in preventing transmission of AWD and chlorine is an effective chemical to disinfect water supplies. The US Centers for Disease Control and Prevention collaborated with the WASH Cluster and the United Nations Children’s Fund, Ethiopia, to provide technical assistance to the Somali Regional Water Bureau to improve chlorination of drinking water supplies and quickly assess water quality improvements in Jijiga town, Fafan Zone. Timely sharing of surveillance and case investigation data allowed for the identification of gaps within the water supply system in Jijiga and implementation of centralized and decentralized chlorination interventions and monitoring systems. Pilot use of a rapid assessment to determine residual chlorine levels at various points in the city helped improve chlorination intervention impact. This work illustrates that rapid community-level water quality improvements can be implemented and assessed quickly to improve interventions during outbreaks.

Coronavirus disease 2019 (COVID-19) has been reported nationwide among meat processing facility workers (1). In late April 2020, through flyers and text messages, workers at a Nebraska meat processing facility were invited by the facility, in partnership with the Nebraska Department of Health and Human Services, to be tested for current SARS-CoV-2, the virus that causes COVID-19, at their worksite, free of charge. Specimens were analyzed using reverse transcription–polymerase chain reaction (RT-PCR) by a contracting laboratory. This investigation was determined by CDC to be public health surveillance.* Among 1,216 Nebraska-resident meat processing facility workers tested, 375 (31%) had positive results. During May 8–25, case investigators attempted to interview the 349 workers who had positive test results and available phone numbers; five refused, 99 were not reached after five attempts, and four did not report symptom status, leaving 241 (69%) of the attempted interviews for analysis.

Diarrheal illness, a common occurrence among people living with human immunodeficiency virus (PLHIV), is largely preventable through access to safe drinking water quality, sanitation, and hygiene (WASH) facilities. We examined WASH characteristics among households with and without HIV-positive residents enrolled in the Global Enteric Multicenter Study (GEMS) in rural Western Kenya. Using univariable logistic regression, we examined differences between HIV-positive and HIV-negative households in regard to WASH practices. Among HIV-positive households, we explored the relationship between the length of time knowing their HIV status and GEMS enrollment. No statistically significant differences were apparent in the WASH characteristics among HIV-positive and HIV-negative households. However, we found differences in the WASH characteristics among HIV-positive households who were aware of their HIV status >/= 30 days before enrollment compared with HIV-positive households who found out their status < 30 days before enrollment or thereafter. Significantly more households aware of their HIV-positive status before enrollment reported treating their drinking water (odds ratio [OR] confidence interval [CI]: 2.34 [1.12, 4.86]) and using effective water treatment methods (OR [CI]: 9.6 [3.09, 29.86]), and had better drinking water storage practices. This suggests that within this region of Kenya, HIV programs are effective in promoting the importance of practicing positive WASH-related behaviors among PLHIV.

Evaluation of a Water and Hygiene Project in Health-Care Facilities in Siaya County, Kenya, 2016.

Current World Health Organization (WHO) guidelines recommend cryptococcal antigen (CrAg) screening in blood among those human immunodeficiency virus (HIV)-infected persons not receiving effective antiretroviral therapy (ART), with CD4 values <100 cells/µL, and to consider testing those not on ART with CD4 values between 100–200 cells/µL [1]. This recommendation is based on prior studies demonstrating that a “screen-and-treat” program identifying CrAg-positive persons and giving preemptive fluconazole therapy, in combination with an ART adherence intervention, prevents invasive cryptococcal disease and death [2].

In August 2015, an outbreak of cholera was reported in Tanzania. In cholera-affected areas of urban Dar es Salaam and Morogoro, many households obtained drinking water from vendors, who sold water from tanks ranging in volume from 1,000 to 20,000 L. Water supplied by vendors was not adequately chlorinated. The Tanzanian Ministry of Health, Community Development, Gender, Elderly and Children and the U.N. Children's Fund, Tanzania, collaborated to enroll and train vendors to treat their water with 8.68-g sodium dichloroisocyanurate tablets. The CDC provided monitoring and evaluation support. Vendors were provided a 3-month supply of chlorine tablets. A baseline assessment and routine monitoring were conducted by ward environmental health officers. Approximately 3 months after chlorine tablet distribution, an evaluation of the program was conducted. The evaluation included a full enumeration of all vendors, an in-depth survey with half of the vendors enumerated, and focus group discussions. In total, 797 (88.9%) vendors were included in the full enumeration and 392 in the in-depth survey. Free residual chlorine (FRC) was detected in 12.0% of tanks at baseline and 69.6% of tanks during the evaluation; however, only 17.4% of these tanks had FRC >/= 0.5 mg/L. The results suggest high acceptability and use of the chlorine tablets by water vendors. However, given variation in the water source used and longer storage times, dosing could be increased in future programming. Bulk chlorination using chlorine tablets offers an efficient community-level approach to treating water closer to the point of use.

BACKGROUND: Cryptococcal meningitis accounts for 15% of AIDS-related mortality. Cryptococcal antigen (CrAg) is detected in blood weeks before onset of meningitis, and CrAg positivity is an independent predictor of meningitis and death. CrAg screening for patients with advanced HIV and preemptive treatment is recommended by the World Health Organization, though implementation remains limited. Our objective was to evaluate costs and mortality reduction (lives saved) from a national CrAg screening program across Uganda. METHODS: We created a decision analytic model to evaluate CrAg screening. CrAg screening was considered for those with a CD4<100 cells/muL per national and international guidelines, and in the context of a national HIV test-and-treat program where CD4 testing was not available. Costs (2016 USD) were estimated for screening, preemptive therapy, hospitalization, and maintenance therapy. Parameter assumptions were based on large prospective CrAg screening studies in Uganda, and clinical trials from sub Saharan Africa. CrAg positive (CrAg+) persons could be: (a) asymptomatic and thus eligible for preemptive treatment with fluconazole; or (b) symptomatic with meningitis with hospitalization. RESULTS: In the base case model for 1 million persons with a CD4 test annually, 128,000 with a CD4<100 cells/muL were screened, and 8,233 were asymptomatic CrAg+ and received preemptive therapy. Compared to no screening and treatment, CrAg screening and treatment in the base case cost $3,356,724 compared to doing nothing, and saved 7,320 lives, for a cost of $459 per life saved, with the $3.3 million in cost savings derived from fewer patients developing fulminant meningitis. In the scenario of a national HIV test-and-treat program, of 1 million HIV-infected persons, 800,000 persons were screened, of whom 640,000 returned to clinic, and 8,233 were incident CrAg positive (CrAg prevalence 1.4%). The total cost of a CrAg screening and treatment program was $4.16 million dollars, with 2,180 known deaths. Conversely, without CrAg screening, the cost of treating meningitis was $3.09 million dollars with 3,806 deaths. Thus, despite the very low CrAg prevalence of 1.4% in the general HIV-infected population, and inadequate retention-in-care, CrAg screening averted 43% of deaths from cryptococcal meningitis at a cost of $662 per death averted. CONCLUSION: CrAg screening and treatment programs are cost-saving and lifesaving, assuming preemptive treatment is 77% effective in preventing death, and could be adopted and implemented by ministries of health to reduce mortality in those with advanced HIV disease. Even within HIV test-and-treat programs where CD4 testing is not performed, and CrAg prevalence is only 1.4%, CrAg screening is cost-effective.

BACKGROUND: HIV-infected persons with cryptococcal antigenemia (CrAg) are at high risk for meningitis or death. We evaluated the effect of CrAg screening and pre-emptive fluconazole therapy, as an adjunct to antiretroviral therapy (ART), on six-month survival among persons with advanced HIV disease. METHODS: We enrolled HIV-infected, ART-naive eligible participants with <100 CD4 cells/microL, in a stepped-wedge, cluster-randomized trial from July 2012 - December 2014 at 17 Ugandan clinics. Clinics participated in a prospective observational phase, followed by an interventional phase with lab-based, reflexive CrAg screening of residual CD4 count plasma. Asymptomatic CrAg-positive participants received preemptive fluconazole therapy for ten weeks. We assessed six-month survival using Cox-regression, adjusting for nadir CD4, calendar time, and stepped-wedge steps. RESULTS: We included 1,280 observational and 2,108 interventional participants, of whom 9.3% (195/2,108) were CrAg-positive. CD4-, time-, and stepped-wedge-adjusted analyses demonstrated no difference in survival in the observational vs the interventional arms (HR = 1.34; 95% CI, 0.86-2.10; P = 0.20), including when the analysis was limited to persons who started ART (HR=1.11; 95% CI, 0.62 - 1.79, P=0.86) However, six-month mortality of participants with CrAg titers <1:160 and CrAg-negative patients did not differ. Patients with CrAg titers >/=1:160 had 2.6-fold higher six-month mortality than patients with titers <1:160. CONCLUSION: We observed no overall survival benefit of the lab-based reflexive CrAg screen-and-treat intervention. However, preemptive antifungal therapy for asymptomatic cryptococcosis appeared to be effective in patients with CrAg titer <1:160. A more aggressive approach may be required for persons with CrAg titer >/=1:160.This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Access to safe drinking water and improved hygiene are essential for preventing diarrheal diseases in low- and middle-income countries. Integrating water treatment and hygiene products into antenatal clinic care can motivate water treatment and handwashing among pregnant women. Free water hygiene kits (water storage containers, sodium hypochlorite water treatment solution, and soap) and refills of water treatment solution and soap were integrated into antenatal care and delivery services in Machinga District, Malawi, resulting in improved water treatment and hygiene practices in the home and increased maternal health service use. To determine whether water treatment and hygiene practices diffused from maternal health program participants to friends and relatives households in the same communities, we assessed the practices of 106 nonpregnant friends and relatives of these new mothers at baseline and 1-year follow-up. At follow-up, friends and relatives were more likely than at baseline to have water treatment products observable in the home (33.3% vs. 1.2%, p < 0.00001) and detectable free chlorine residual in their water, confirming water treatment (35.7% vs. 1.4%; p < 0.00001). Qualitative data from in-depth interviews also suggested that program participants helped motivate adoption of water treatment and hygiene behaviors among their friends and relatives.

Many health care facilities (HCFs) and households in low-and-middle-income countries have inadequate access to water for hygiene and consumption. To address these problems, handwashing and drinking water stations were installed in 53 HCFs with prevention-of-mother-to-child-transmission of HIV programs in Kenya in 2005, and hygiene education was provided to health workers and clinic clients. To assess this program, we selected a random sample of 30 HCFs, observed the percentage of handwashing and drinking water stations that were functional and in use, and after that interviewed health providers and clients about hygiene and water treatment. Results indicated that, six years after implementation, 80.0% of HCFs had at least one functional handwashing station and 83.3% had at least one functional drinking water station. In addition, 60% of HCFs had soap at >/= one handwashing stations, and 23.3% had >/= one container with detectable free chlorine. Of 299 clients (mothers with >/= one child under five), 57.2% demonstrated proper water treatment knowledge, 93.3% reported ever using water treatment products, 16.4% had detectable chlorine residual in stored water, and 89.0% demonstrated proper handwashing technique. Six years after program implementation, although most HCFs had water stations and most clients could demonstrate proper handwashing technique, water stored in most clinics and homes was not treated.

BACKGROUND: HIV-infected persons with detectable cryptococcal antigen (CrAg) in blood have increased morbidity and mortality compared with HIV-infected persons who are CrAg-negative. This study examined neurocognitive function among persons with asymptomatic cryptococcal antigenemia. METHODS: Participants from three prospective HIV cohorts underwent neurocognitive testing at the time of antiretroviral therapy (ART) initiation. Cohorts included persons with cryptococcal meningitis (N = 90), asymptomatic CrAg + (N = 87), and HIV-infected persons without central nervous system infection (N = 125). Z-scores for each neurocognitive test were calculated relative to an HIV-negative Ugandan population with a composite quantitative neurocognitive performance Z-score (QNPZ-8) created from eight tested domains. Neurocognitive function was measured pre-ART for all three cohorts and additionally after 4 weeks of ART (and 6 weeks of pre-emptive fluconazole) treatment among asymptomatic CrAg + participants. RESULTS: Cryptococcal meningitis and asymptomatic CrAg + participants had lower median CD4 counts (17 and 26 cells/muL, respectively) than the HIV-infected control cohort (233 cells/muL) as well as lower Karnofsky performance status (60 and 70 vs. 90, respectively). The composite QNPZ-8 for asymptomatic CrAg + (-1.80 Z-score) fell between the cryptococcal meningitis cohort (-2.22 Z-score, P = 0.02) and HIV-infected controls (-1.36, P = 0.003). After four weeks of ART and six weeks of fluconazole, the asymptomatic CrAg + cohort neurocognitive performance improved (-1.0 Z-score, P < 0.001). CONCLUSION: Significant deficits in neurocognitive function were identified in asymptomatic CrAg + persons with advanced HIV/AIDS even without signs or sequelae of meningitis. Neurocognitive function in this group improves over time after initiation of pre-emptive fluconazole treatment and ART, but short term adherence support may be necessary.

BACKGROUND: Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. Global burden estimates are crucial to guide prevention strategies and to determine treatment needs, and we aimed to provide an updated estimate of global incidence of HIV-associated cryptococcal disease. METHODS: We used 2014 Joint UN Programme on HIV and AIDS estimates of adults (aged >15 years) with HIV and antiretroviral therapy (ART) coverage. Estimates of CD4 less than 100 cells per muL, virological failure incidence, and loss to follow-up were from published multinational cohorts in low-income and middle-income countries. We calculated those at risk for cryptococcal infection, specifically those with CD4 less than 100 cells/muL not on ART, and those with CD4 less than 100 cells per muL on ART but lost to follow-up or with virological failure. Cryptococcal antigenaemia prevalence by country was derived from 46 studies globally. Based on cryptococcal antigenaemia prevalence in each country and region, we estimated the annual numbers of people who are developing and dying from cryptococcal meningitis. FINDINGS: We estimated an average global cryptococcal antigenaemia prevalence of 6.0% (95% CI 5.8-6.2) among people with a CD4 cell count of less than 100 cells per muL, with 278 000 (95% CI 195 500-340 600) people positive for cryptococcal antigen globally and 223 100 (95% CI 150 600-282 400) incident cases of cryptococcal meningitis globally in 2014. Sub-Saharan Africa accounted for 73% of the estimated cryptococcal meningitis cases in 2014 (162 500 cases [95% CI 113 600-193 900]). Annual global deaths from cryptococcal meningitis were estimated at 181 100 (95% CI 119 400-234 300), with 135 900 (75%; [95% CI 93 900-163 900]) deaths in sub-Saharan Africa. Globally, cryptococcal meningitis was responsible for 15% of AIDS-related deaths (95% CI 10-19). INTERPRETATION: Our analysis highlights the substantial ongoing burden of HIV-associated cryptococcal disease, primarily in sub-Saharan Africa. Cryptococcal meningitis is a metric of HIV treatment programme failure; timely HIV testing and rapid linkage to care remain an urgent priority.

On August 15, 2015, the Tanzanian Ministry of Health, Community Development, Gender, Elderly and Children (MOHCDGEC) was notified about a case of acute watery diarrhea with severe dehydration in a patient in Dar es Salaam. Vibrio cholerae O1, biotype El tor, serotype Ogawa, was isolated from the patient’s stool and an investigation was initiated. MOHCDGEC defined a suspected cholera case as the occurrence of severe dehydration or death from acute watery diarrhea in a person aged ≥5 years, or acute, profuse watery diarrhea with or without vomiting in a person aged ≥2 years in a region with an active cholera outbreak. A confirmed cholera case was defined as isolation of V. cholerae O1 from the stool of a person with suspected cholera. Tanzania’s first reported cholera epidemic was in 1974 with intermittent outbreaks since then; the largest epidemic occurred in 1997, with 40,249 cases and 2,231 deaths (case fatality rate [CFR] was 5.5%) (1). | As of November 26, 2016, the current epidemic continues, affecting 23 (92%) of 25 regions in mainland Tanzania (excluding the Zanzibar archipelago), with a cumulative reported case count of 23,258 and a cumulative CFR of 1.5%. The median number of reported cholera cases per week was 271 (range = 5–1,240) (Figure). Approximately half of all reported cases have been from four regions: Dar es Salaam (5,104; 22%), Morogoro (3,177; 14%), Mwanza (2,311; 10%), and Mara (2,299; 10%). Of 511 stool specimens tested during August 17, 2015–March 18, 2016 at the National Health Laboratory-Quality Assurance Training Center in Dar es Salaam, 268 (52%) were positive for V. cholerae; all specimens were serogroup O1, biotype El tor, serotype Ogawa. Antimicrobial resistance (AMR) testing revealed sensitivity to cotrimoxazole, ceftriaxone, tetracycline, ciprofloxacin, and chloramphenicol, and resistance to nalidixic acid and ampicillin.

In the developing world, fetching water for drinking and other household uses is a substantial burden that affects water quantity and quality in the household. We used logistic regression to examine whether reported household water fetching times were a risk factor for moderate-to-severe diarrhea (MSD) using case-control data of 3,359 households from the Global Enterics Multi-Center Study in Kenya in 2009-2011. We collected additional global positioning system (GPS) data for a subset of 254 randomly selected households and compared GPS-based straight line and actual travel path distances to fetching times reported by respondents. GPS-based data were highly correlated with respondent-provided times (Spearman correlation coefficient = 0.81, P < 0.0001). The median estimated one-way distance to water source was 200 m for cases and 171 for controls (Wilcoxon rank sums/Mann-Whitney P = 0.21). A round-trip fetching time of > 30 minutes was reported by 25% of cases versus 15% of controls and was significantly associated with MSD where rainwater was not used in the last 2 weeks (odds ratio = 1.97, 95% confidence interval = 1.56-2.49). These data support the United Nations definition of access to an improved water source being within 30 minutes total round-trip travel time.

There is limited understanding of the epidemiology of meningitis among human immunodeficiency virus (HIV)-infected populations in sub-Saharan Africa. We conducted a prospective cohort study of HIV-infected adults with suspected meningitis in Uganda, to comprehensively evaluate the etiologies of meningitis. Intensive cerebrospiral fluid (CSF) testing was performed to evaluate for bacterial, viral, fungal, and mycobacterial etiologies, including neurosyphilis,16s ribosomal DNA (rDNA) polymerase chain reaction (PCR) for bacteria, Plex-ID broad viral assay, quantitative-PCR for HSV-1/2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Toxoplasma gondii; reverse transcription-PCR (RT-PCR) for Enteroviruses and arboviruses, and Xpert MTB/RIF assay. Cryptococcal meningitis accounted for 60% (188 of 314) of all causes of meningitis. Of 117 samples sent for viral PCR, 36% were EBV positive. Among cryptococcal antigen negative patients, the yield of Xpert MTB/RIF assay was 22% (8 of 36). After exclusion of cryptococcosis and bacterial meningitis, 61% (43 of 71) with an abnormal CSF profile had no definitive diagnosis. Exploration of new TB diagnostics and diagnostic algorithms for evaluation of meningitis in resource-limited settings remains critical.

BACKGROUND: Strategies to prevent gastric cancer by decreasing Helicobacter pylori infections in high-prevalence, low-income countries could include a population-based "screen and treat" eradication program. METHODS: We tested residents of two rural villages for H. pylori infection using urea breath test (UBT), treated infected persons using directly observed therapy (DOT), retested for cure, and retested after 1 year later for H. pylori infection. FINDINGS: We tested 1,065 (92%) of 1153 residents from two villages in rural Bolivia. Baseline H. pylori prevalence was 80% (95% confidence interval [CI]: 78-84). Age-specific cure rates were similar (≥92%) after DOT. Among those cured, 12% (95% CI: 8-15) had recurrent infection. Age-specific annual H. pylori recurrence rates for combined villages were 20% (95% CI: 10-29) in persons <5 years, 20% (95% CI: 10-29) in 5-9 years, 8% (95% CI: 1-15) in 10-14 years, and 8% (95% CI: 4-12) in persons ≥15 years. Compared with the referent population, those ≥15 years, recurrent infections were significantly more likely in children <5 years (odds ratios [OR] 2.7, 95% CI: 1.2-5.8) and 5-9 years (OR 2.7, 95% CI: 1.4-5.1). INTERPRETATION: Children <10 years had high H. pylori recurrence rates following a population-based screen and treat program; this H. pylori eradication strategy may not be feasible in high-prevalence, low-income settings.

PROBLEM/CONDITION: Since 1971, CDC, the Environmental Protection Agency (EPA), and the Council of State and Territorial Epidemiologists have collaborated on the Waterborne Disease and Outbreak Surveillance System (WBDOSS) for collecting and reporting data related to occurrences and causes of waterborne disease outbreaks associated with drinking water. This surveillance system is the primary source of data concerning the scope and health effects of waterborne disease outbreaks in the United States. REPORTING PERIOD: Data presented summarize 48 outbreaks that occurred during January 2007--December 2008 and 70 previously unreported outbreaks. DESCRIPTION OF SYSTEM: WBDOSS includes data on outbreaks associated with drinking water, recreational water, water not intended for drinking (WNID) (excluding recreational water), and water use of unknown intent (WUI). Public health agencies in the states, U.S. territories, localities, and Freely Associated States are primarily responsible for detecting and investigating outbreaks and reporting them voluntarily to CDC by a standard form. Only data on outbreaks associated with drinking water, WNID (excluding recreational water), and WUI are summarized in this report. Outbreaks associated with recreational water are reported separately. RESULTS: A total of 24 states and Puerto Rico reported 48 outbreaks that occurred during 2007--2008. Of these 48 outbreaks, 36 were associated with drinking water, eight with WNID, and four with WUI. The 36 drinking water--associated outbreaks caused illness among at least 4,128 persons and were linked to three deaths. Etiologic agents were identified in 32 (88.9%) of the 36 drinking water--associated outbreaks; 21 (58.3%) outbreaks were associated with bacteria, five (13.9%) with viruses, three (8.3%) with parasites, one (2.8%) with a chemical, one (2.8%) with both bacteria and viruses, and one (2.8%) with both bacteria and parasites. Four outbreaks (11.1%) had unidentified etiologies. Of the 36 drinking water--associated outbreaks, 22 (61.1%) were outbreaks of acute gastrointestinal illness (AGI), 12 (33.3%) were outbreaks of acute respiratory illness (ARI), one (2.8%) was an outbreak associated with skin irritation, and one (2.8%) was an outbreak of hepatitis. All outbreaks of ARI were caused by Legionella spp. A total of 37 deficiencies were identified in the 36 outbreaks associated with drinking water. Of the 37 deficiencies, 22 (59.5%) involved contamination at or in the source water, treatment facility, or distribution system; 13 (35.1%) occurred at points not under the jurisdiction of a water utility; and two (5.4%) had unknown/insufficient deficiency information. Among the 21 outbreaks associated with source water, treatment, or distribution system deficiencies, 13 (61.9%) were associated with untreated ground water, six (28.6%) with treatment deficiencies, one (4.8%) with a distribution system deficiency, and one (4.8%) with both a treatment and a distribution system deficiency. No outbreaks were associated with untreated surface water. Of the 21 outbreaks, 16 (76.2%) occurred in public water systems (drinking water systems under the jurisdiction of EPA regulations and water utility management), and five (23.8%) outbreaks occurred in individual systems (all of which were associated with untreated ground water). Among the 13 outbreaks with deficiencies not under the jurisdiction of a water system, 12 (92.3%) were associated with the growth of Legionella spp. in the drinking water system, and one (7.7%) was associated with a plumbing deficiency. In the two outbreaks with unknown deficiencies, one was associated with a public water supply, and the other was associated with commercially bottled water. The 70 previously unreported outbreaks included 69 Legionella outbreaks during 1973--2000 that were not reportable previously to WBDOSS and one previously unreported outbreak from 2002. INTERPRETATION: More than half of the drinking water--associated outbreaks reported during the 2007--2008 surveillance period were associated with untreated or inadequately treated ground water, indicating that contamination of ground water remains a public health problem. The majority of these outbreaks occurred in public water systems that are subject to EPA's new Ground Water Rule (GWR), which requires the majority of community water systems to complete initial sanitary surveys by 2012. The GWR focuses on identification of deficiencies, protection of wells and springs from contamination, and providing disinfection when necessary to protect against bacterial and viral agents. In addition, several drinking water--associated outbreaks that were related to contaminated ground water appeared to occur in systems that were potentially under the influence of surface water. Future efforts to collect data systematically on contributing factors associated with drinking water outbreaks and deficiencies, including identification of ground water under the direct influence of surface water and the criteria used for their classification, would be useful to better assess risks associated with ground water. During 2007--2008, Legionella was the most frequently reported etiology among drinking water--associated outbreaks, following the pattern observed since it was first included in WBDOSS in 2001. However, six (50%) of the 12 drinking water--associated Legionella outbreaks were reported from one state, highlighting the substantial variance in outbreak detection and reporting across states and territories. The addition of published and CDC-investigated legionellosis outbreaks to the WBDOSS database clarifies that Legionella is not a new public health issue. During 2009, Legionella was added to EPA's Contaminant Candidate List for the first time. PUBLIC HEALTH ACTIONS: CDC and EPA use WBDOSS surveillance data to identify the types of etiologic agents, deficiencies, water systems, and sources associated with waterborne disease outbreaks and to evaluate the adequacy of current technologies and practices for providing safe drinking water. Surveillance data also are used to establish research priorities, which can lead to improved water quality regulation development. Approximately two thirds of the outbreaks associated with untreated ground water reported during the 2007--2008 surveillance period occurred in public water systems. When fully implemented, the GWR that was promulgated in 2006 is expected to result in decreases in ground water outbreaks, similar to the decreases observed in surface water outbreaks after enactment of the Surface Water Treatment Rule in 1974 and its subsequent amendments. One third of drinking water--associated outbreaks occurred in building premise plumbing systems outside the jurisdiction of water utility management and EPA regulations; Legionella spp. accounted for >90% of these outbreaks, indicating that greater attention is needed to reduce the risk for legionellosis in building plumbing systems. Finally, a large communitywide drinking water outbreak occurred in 2008 in a public water system associated with a distribution system deficiency, underscoring the importance of maintaining and upgrading drinking water distribution system infrastructure to provide safe water and protect public health.

Stopping the spread of the cholera epidemic in Haiti required engaging community health workers (CHWs) in prevention and treatment activities. The Centers for Disease Control and Prevention collaborated with the Haitian Ministry of Public Health and Population to develop CHW educational materials, train >1,100 CHWs, and evaluate training efforts.